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Sickle Cell News Articles
News Articles from Past New Updates
April 2008
Doctors at Johns Hopkins say Pamela Newton is the first
adult worldwide to be cured of sickle cell disease using an experimental bone
marrow transplant.
Fifteen months ago, the pain from Pamela Newton's sickle cell disease was
excruciating. She spent more time in the hospital than in her Capitol Heights
apartment. She was on 15 pain pills a day, all heavy narcotics. She was bleeding
regularly and needed daily transfusions of platelets.Today, doctors at Johns
Hopkins Hospital say that Newton is one of the first adults in the world to
be cured of sickle cell disease - and the first using an experimental bone
marrow transplant that could cure thousands like her who have been told they
will never get better.
Word of a breakthrough gives hope to the roughly 80,000 Americans - and millions
around the world - who suffer from this debilitating and usually fatal disease,
which is predominant among African-Americans and Hispanics.Bone marrow
transplants have been used to treat sickle cell disease for 20 years - but
almost all of the 200 cured have been children. The treatments - high doses of
chemicals that knock out the patient's own marrow before the transplant - are so
toxic that adults with sickle cell-induced organ damage would be unlikely to
survive them.
Brodsky said his team's procedure, developed by Dr. Ephraim Fuchs and Dr. Leo
Luznik, is less toxic. They say they no longer believe they have to destroy as
much of the patient's marrow as they once did - so they administer just enough
chemotherapy to suppress the immune system. That dose keeps patients from
rejecting the new marrow without harming their organs.This change allows
transplants for adults, as well as children. Because the procedure occurs later
in life, it relieves parents of the burden of making the decision for their
youngsters (even in children, the sickle-cell transplant mortality rate is 5
percent to 10 percent). Instead, it allows the adult patient to see how severe
the disease is before deciding whether to have a transplant.
Another transplant obstacle has been finding a perfect bone marrow match - a
full sibling's marrow provides the best chance. But there's only a 25 percent
chance that even a full sibling will be a match. And since sickle cell is
inherited, siblings may also have the disease. That leaves about a 10 percent
chance that a patient will find a suitable donor. Brodsky's procedure requires
just a half-match - meaning that children and parents of the patient could be
suitable donors.
Three days after the transplant, the patient is given a high dose of a drug
called cyclophosphamide. Just as the bone marrow is taking root, the drug kills
off the donor's lymphocytes - blood cells that are part of the immune system.
The cyclophosphamide spares the donor's stem cells and allows them to establish
new blood cells and a new immune system. The nascent immune system is re-trained
to see the patient's body as friend, not foe. This prevents the patient from
rejecting the transplanted bone marrow - and prevents the newly developing
immune system from http://www.baltimoresun.com/news/health/bal-te.sickle30mar30,0,6112155.story
22-month-old son of Jazz's Boozer
battles sickle cell, shows dad how recovery is done
The 22-month-old hugs the ball to his chest as he bounces
around the room before his dad sweeps him up for a father-son grin and
giggle.Carlos Boozer has had to recover from a host of injuries that come with
being a power forward in the NBA, yet he can only imagine what his son has
endured in the last year.
Carmani has had chemotherapy, made countless trips to the
doctor and spent weeks in the hospital before and after a bone-marrow transplant
that his parents hope wiped out his sickle cell anemia.Six months later, Carmani
is still free of the blood disorder, but Boozer and his wife, CeCe, have another
six months of angst before knowing whether the procedure was a
success."We're just looking forward to that day when he's clear
completely," Boozer said.
They just aren't sure when or if that day will come. If
it does, the Boozers will know that they made the right call in a series of
difficult choices that ultimately led to deciding on a transplant and a search
for the right donor. They found one by producing their own through in-vitro
fertilization.
Two of the healthy embryos they created were implanted
and Cece Boozer had twin boys last July. After Carmani had chemotherapy to
attack his sickle-cell producing bone marrow, he was injected with stem cells
from one twin's umbilical cord to stimulate the growth of new bone marrow in the
hope it will produce healthy blood cells. http://www.usatoday.com/sports/basketball/2008-03-27-2096859841_x.htm
Cell-phone microscope takes diagnostics into underserved
communities
What began as a relatively simple class project in Prof. Dan Fletcher's
undergraduate optics and microscopy course at the University of California at
Berkeley has resulted in the development of a handheld microscopic imaging and
transmission device that may have implications for healthcare in Third World,
rural, and other underserved communities.
When Fletcher challenged his students to combine current readily available
technologies with a potential application that could improve healthcare in
underdeveloped countries, little did he know that his students would respond
with such enthusiasm and ingenuity. They took a standard cell phone and modified
it with a series of off-the-shelf lenses to achieve 5x-60x magnification of a
blood or tissue sample, utilizing the phone's internal camera to capture and
transmit the resulting images (see Figure).
"I was trying to give them something relevant to think about," says
Fletcher, who is associate professor of bioengineering. "In developing
world-health efforts there is a growing realization that smart phones can do a
lot for healthcare."
The initial prototype of the cell-phone microscope--dubbed "Cellscope"--utilizes
a Nokia cell phone with an embedded 3.1 megapixel camera. The phone's pocket
holster provides the mount for the optical train. Illumination is provided by
several white-light LEDs in a ring-illuminator design, and the detection sensors
are based on standard CCD/CMOS chips. Once captured, the images are transmitted
to a laptop using a Bluetooth attachment to the phone. Total cost of the first
prototype, built from off-the-shelf components, was $75. http://www.laserfocusworld.com/display_article/324816/12/none/none/TECHN/Cell-phone-microscope-takes-diagnostics-into-underserved-communitie
Medical trial to test Teflon-like liquid as a blood
replacement
200-patient human trial about to start
at the University of Miami School of Medicine into Oxycyte, a Teflon-like liquid
that carries four times the oxygen levels of real, red blood cells to brain
tissue damaged by traumatic injury. Without that continuous flow of oxygen,
brain cells can die within hours. If
it succeeds in civilian trials here, it could be on the battlefield in Iraq in a
year or two to help soldiers who suffer traumatic brain injury from IEDs -
improvised explosive devices. TBI has been called "the signature
wound" of the Iraq war, with 1,882 cases treated to date. The Department of
Defense has signaled its interest in Oxycyte by funding $1.9 million of the $4
million cost of the trials.
If we can interrupt the cascade of cell death during the hours
and days after the initial brain injury, we can save someone from a lifetime of
disability," says Dr. M. Ross Bullock, director of clinical neurotrauma at
the University of Miami School of Medicine. He's the lead investigator on the
trial, which will take place over the next year at the Miami Project to Cure
Paralysis. At the same time, other researchers at the Miami Project will be
studying Oxycyte for use in spinal cord injury, says Dr. W. Dalton Dietrich, the
project's scientific director. "If we can improve
oxygen flow to the compromised area of the spinal cord, and start early enough,
some patients can probably benefit," he says.
Other doctors are researching whether Oxycyte can help with
stroke, heart attack, cancer, sickle cell anemia, even hard-to-heal diabetic
wounds and bed sores. They acknowledge it sounds too good to be true. "If
this works, it will be very big," says Dr. Harvey Klein, chief of the
Department of Transfusion Medicine at the National Institutes of Health, who is
not involved in the university trials. "But my enthusiasm is tempered by 20
years of experience with these drugs where they haven't worked.
"The proof of the pudding will be in the clinical
trials." Dietrich expresses hope: "We do so many
complicated things trying to heal injuries. But the simplest way is to improve
the flow of blood and oxygen. At the end of the day, if tissue is starved of
oxygen, it dies."
http://www.pressofatlanticcity.com/114/story/114213.html
IVF with Genetic and Chromosomal Testing of Embryos Can Improve Chances of
Having a Healthy Child
In vitro fertilization (IVF) combined with a procedure called Preimplantation
Genetic Diagnosis (PGD) can improve a woman's chances of having a healthy baby
when there is a family history of inherited genetic diseases or conditions, or
if a patient has experienced miscarriages caused by embryo chromosomal
abnormality.
Embryo biopsy with PGD is a procedure utilized in conjunction with IVF to
screen for genetic and/or chromosomal problems before an embryo is selected for
uterine implantation. This is also called "pre-pregnancy diagnosis". A
number of genetic disorders and/or chromosomal abnormalities can be identified
through PGD including Muscular Dystrophy, Hemophilia, Sickle Cell Anemia, Cystic
Fibrosis, Tay Sachs, Fragile X Syndrome, Turner Syndrome, Huntington disease and
Down syndrome.
"PGD allows us to differentiate abnormal embryos from the normal
embryos, so that only normal embryos are transferred to the uterus," said
Dr. Andrew Levi," a board certified reproductive endocrinologist and
founder of Park Avenue Fertility and Reproductive Medicine in Trumbull,
Connecticut. "In select patients, IVF with PGD can significantly decrease
miscarriage rates and help women at risk for miscarriage achieve a successful
pregnancy."
Dr. Levi reports that the majority of couples who proceed with IVF in
conjunction with PGD either have experienced recurrent miscarriages; prior
unexplained IVF failures; have conceived with a fetus or child with a chromosome
abnormality; or have an identifiable or inheritable genetic medical conditions.
IVF entails stimulation of a woman's ovaries to obtain multiple eggs,
subsequent removal of the eggs from the woman's body, fertilization of the eggs
with the patient's partner's sperm, and transfer of the fertilized eggs
(embryos) back to the woman's uterus. Embryo biopsy with PGD is performed
typically three days after fertilization and before embryo transfer.
http://www.prweb.com/releases/2008/3/prweb785124.htm
For more information
http://www.emedicine.com/MED/topic3520.htm
http://www.hfea.gov.uk/en/910.html
March 2008
NHLBI Announcement: Institute to Realign its Sickle Cell
Disease Research Program
The National Heart, Lung, and Blood Institute (NHLBI) announced today a
comprehensive and innovative restructuring of its research program in sickle
cell disease (SCD).SCD is a serious inherited blood disorder that most
commonly affects people with origins in Africa, Latin America, the Middle
East, or the Mediterranean.Since 1972, the NHLBI has developed and maintained
a major research effort to improve the lives of individuals with SCD.The
studies have led to a number of effective approaches for the management and
treatment of the disease, and today’s patients live longer and have a better
quality of life than was the case in previous generations.However, there is no
cure for SCD, and therapies that exist do not benefit all patients.
The recent issuance of the Institute’s Strategic Plan (http://apps.nhlbi.nih.gov/strategicplan/)
and the scheduled renewal of the Comprehensive Sickle Cell Centers (CSCC)
program provided an opportune time to rigorously assess the NHLBI program in
SCD.The National Heart, Lung, and Blood Advisory Council conducted an
extensive review of the Institute’s research and training portfolio in SCD,
taking into account responses received to a public solicitation for input from
patients and lay and professional constituencies about the top scientific and
clinical priorities.A detailed report on the Council’s findings and
deliberations can be found at http://www.nhlbi.nih.gov/meetings/workshops/Sickle-Cell-Announcement.htm.
Recommendations include the following.
- Basic science — Research should focus on disease mechanisms; new
treatment approaches; genes and genetics; molecular biology and
biomarkers; vascular biology; erythropoiesis and red blood cell biology;
and animal models.Progress in this area will require stimulation of
investigator-initiated research applications, with careful attention to
appropriate peer review, and expanded involvement of scientists from areas
other than hematology.
- Translational and clinical research — Emphasis should be placed on
pain pathophysiology and management; fetal hemoglobin induction; trials of
promising alternatives to hydroxyurea; approaches targeting disease
pathophysiology; curative therapies; and prediction, prevention, and
management of severe manifestations and end-organ damage.The NHLBI should
provide research resources such as databases for genotype–phenotype data
and repositories for biological samples, encourage resource-sharing among
investigators, and assist investigators in bringing clinically relevant
basic science discoveries to the point where they are ready for human
trials.
- Participation in clinical research — The Institute should increase the
pool of potential participants for interventional and observational
studies and to provide opportunities for geographically broad
participation by individuals and investigators in research.
- Translation and dissemination to the community — Timely and thorough
application of research findings should be promoted through development of
evidence-based practice guidelines and their widespread dissemination via
educational programs for physicians, other health-care providers, and
patients.
Based on the NHLBAC recommendations, the NHLBI is moving forward with the
following innovations to its SCD portfolio.
- Support for basic research will be expanded through funding of
investigator-initiated grant applications and through NHLBI-initiated RFAs
(requests for applications) focused on the pathophysiology of SCD, the
biology of pain in SCD, fetal hemoglobin switching, and genetic modifiers
of disease expression and progression.
- The Institute will reconfigure the CSCC program into a Basic and
Translational Research Program by funding meritorious projects submitted
in response to the recent RFA (http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-06-008.html).The
program will emphasize fundamental investigations and their translation
into initial studies in humans, as well as community translation to
promote evidence-based clinical practice.SCD Scholars programs for the
career development of young investigators and
Summer-for-Sickle-Cell-Science programs for research training and
mentoring of high-school students also will be supported as part of a
larger effort by the Institute to prepare the next generation of
scientists to advance the field of SCD research.
- The NHLBI has requested comments from its constituency regarding
interest in joining the RAID (Rapid Access to Interventional Development)
program of the National Cancer Institute, which provides contract services
to aid in the translation to the clinic of potential new therapeutic
agents originating in academia (http://grants.nih.gov/grants/guide/notice-files/NOT-HL-08-111.htm).The
RAID offers an avenue for swift progress in evaluation of promising
therapeutic approaches such as innovative drugs to stimulate fetal
hemoglobin production.
- The NHLBI will develop a new Clinical Trials Research Network (CTRN)
designed to open participation in clinical research to a much larger
number of investigators and individuals with SCD than is currently
possible.Structured similarly to the Children’s Oncology Group (http://www.childrensoncologygroup.org/,
which offers clinical trial participation to all eligible subjects and
investigators, the CTRN will, in time, subsume the current SCD Clinical
Research Network (http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-05-006.html).
- The NHLBI will expand its support of genomic research in SCD beyond the
boundaries of current efforts being conducted within the framework of the
CSCCs (http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-05-006.html)
by developing a program like the Framingham SHARe (SNP Health Association
Resource— http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000007.v2.p1)
with contributions of genotypic and phenotypic data from many
investigators and their patients and free access to qualified researchers.
- Finally, the Institute will undertake a focused effort to develop
evidence-based guidelines for the care of individuals with SCD across the
life-span that can be used by health-care practitioners throughout the
world.An educational campaign will be launched, in partnership with the
Sickle Cell Disease Association of America and other patient advocacy
groups and professional organizations, to raise awareness about SCD and
bring nationwide attention to its diagnosis and treatment.
By implementing these recommendations, the NHLBI intends to take advantage
of existing scientific opportunities and make SCD resources more widely
available, better serving both the SCD research and the patient communities.
Inquiries may be directed to:
Susan B. Shurin, M.D.
Deputy Director
National Heart, Lung, and Blood Institute
Building 31, Room 5A48
9000 Rockville Pike
Bethesda, MD 20892- 2486
Telephone: (301) 496-1078
Fax: (301) 402-0818
Email: Shurinsb@nhlbi.nih.gov
http://public.nhlbi.nih.gov/newsroom/home/GetPressRelease.aspx?id=2556
NIH Hydroxyurea Consensus Conference- Panel
finds hydroxyurea treatment is underutilized for sickle cell disease
Improved access to care and education about the treatment are deemed
priorities See the entire conference and view the
consensus statement at http://consensus.nih.gov/2008/2008SickleCellCDC119main.htm
An independent panel convened this week by the NIH concluded that the use
of hydroxyurea for sickle cell patients should be increased in adolescents and
adults. Hydroxyurea was approved by the U.S. Food and Drug Administration for
use in adults with sickle cell anemia in 1998, but provider and patient
concerns have hindered its use, depriving many patients of its proven
benefits. Research has shown that sickle cell patients on this drug experience
fewer pain crises and hospital admissions, and the panel advocated increased
utilization of this drug with appropriate monitoring. Additionally, the panel
concluded that the risks of serious side effects of hydroxyurea appear to be
lower than previously expected. Furthermore, these risks are acceptable when
compared to the risks of untreated sickle cell disease in adolescents and
adults.
"The compelling benefits of hydroxyurea warrant increased adoption of
this drug as a frontline therapy in adults with sickle cell disease,"
reported Dr. Otis Brawley, conference panel chair, Professor of Hematology,
Oncology, Medicine, and Epidemiology at Emory University, and Chief Medical
Officer of the American Cancer Society.
For younger patients, however, safety and efficacy data are limited but
supportive of hydroxyurea treatment. Although the panel was unable to
definitively recommend broad pediatric use of the drug at this time, it is
hoped that results from ongoing clinical trials will help to resolve remaining
questions.
The pain and complications associated with sickle cell disease can have a
profound impact on patients' quality of life, ability to work, and long-term
health and well-being. Sickle cell disease often causes episodes of severe
pain, and decreased life span due to infections, lung problems, and stroke.
Worldwide, millions suffer from sickle cell disease, most commonly people
whose families come from Africa, South or Central America, Caribbean islands,
Mediterranean countries, India, and Saudi Arabia. In the U.S., this inherited
blood disorder affects 50,000 to 100,000 people. In addition, approximately 2
million Americans carry the sickle cell trait, which increases the public
health burden as this disorder is passed on to future generations.
Surveys indicate that a large proportion of patients with sickle cell
disease are ethnic minorities, poor, and from underserved communities. For
many, limited resources and lack of culturally competent clinicians set the
stage for suboptimal care. Recurring pain crises associated with the disease
can severely limit individuals' ability to sustain employment or educational
efforts, aggravating problems with insurance coverage and subsequent
healthcare costs.
"This disease illuminates the limitations of our current healthcare
system," Dr. Brawley noted. "The best way to achieve optimal care
for patients with sickle cell disease is for them to be treated in clinics
specializing in the care of this disease." The panel recognized that many
patients lack a single healthcare provider to direct their sickle cell
management. Instead, there is heavy reliance on emergency and acute care
facilities to treat pain. Dr. Brawley added, "all sickle cell patients
should have a principal healthcare provider, and that provider, if not a
hematologist, should be in frequent consultation with one." Additionally,
patients often "fall through the cracks" when transitioning from
pediatric to adult care. Contributing to this problem is a lack of providers
armed with the knowledge, skills, and experience to effectively manage adults
with sickle cell disease.
In addition to identifying numerous potential barriers to hydroxyurea
treatment at the patient, provider, and systems levels, the panel called for
Medicare or Medicaid coverage of sickle cell patients of all ages.
The panel's complete consensus statement will be available later today at http://consensus.nih.gov/.
The conference was sponsored by the NIH Office of
Medical Applications of Research (OMAR) and the National Heart, Lung, and
Blood Institute, along with other NIH and Department of Health and Human
Services components. This conference was conducted under the NIH Consensus
Development Program, which convenes conferences to assess the available
scientific evidence and develop objective statements on controversial medical
issues.
The 14-member conference panel included experts in the fields of internal
medicine, family practice, hematology, oncology, pediatrics, obstetrics,
nursing, pediatric nursing, social work, pharmacology, pharmacokinetics, and
pain research, mental health, epidemiology, biostatistics, public health, and
health systems research, in addition to a public representative. A complete
listing of the panel members and their institutional affiliations is included
in the draft conference statement. Interviews with panel members can be
arranged by contacting Lisa Ahramjian at 301-496-4999 or AhramjianL@od.nih.gov.
In addition to the material presented at the conference by speakers and the
comments and concerns of conference participants presented during discussion
periods, the panel considered pertinent research from the published literature
and the results of a systematic review of the literature commissioned by OMAR.
The systematic review was prepared through the Agency for Healthcare Research
and Quality (AHRQ) Evidence-based Practice Centers (EPC) program, by the Johns
Hopkins Evidence-based Practice Center. The EPCs develop evidence reports and
technology assessments based on rigorous, comprehensive syntheses and analyses
of the scientific literature, emphasizing explicit and detailed documentation
of methods, rationale, and assumptions. The evidence report on Hydroxyurea
Treatment for Sickle Cell Disease is available at http://www.ahrq.gov/clinic/tp/hydscdtp.htm.
News Stories
http://www.cnn.com/2008/HEALTH/conditions/03/04/sickle.cell.ap/
http://seattlepi.nwsource.com/national/353611_sicklecell04.html
http://www.reuters.com/article/domesticNews/idUSN2747868120080227
For more information, visit
http://consensus.nih.gov/2008/2008SickleCellCDC119main.htm
Resources to Advocate for the Best Educational Resources
for Children with Sickle Cell Disease
We have realized that our state of Minnesota Department of Education does not recognize the neuropsychological impact of
Sickle Cell Disease(SCD) so we are working on getting that changed. As I looked around the country at other states' special education laws, I see it is pretty much the same situation in most states --- the special education category called "Other Health
Disabilities" or "Other Health Impairment" allows for provisions related to mobility, toileting, physical education class
adaptations --- but does NOT show any awareness that SCD (due to low Hg, ischemia, or hypoxia from pulmonary complications) can cause direct adverse impact for some kids on learning and memory, attention-concentration, executive function, motor skills, processing speed . So, we are working with the state special education department in Minnesota to get that changed here.
People who want to work on updating the laws which govern educational opportunities for kids with SCD in their own state can get the relevant Department of Education contact name/numbers from the State Resource Sheets (at
http://www.nichcy.org ). People are welcome to e-mail me or use my handout (attached) on "Educational Impact of Sickle Cell Disease" to advocate for changes in state education regulations.
Another big problem is that some states or insurance providers do not authorize neuropsychological testing of kids with SCD because they are unaware of the research showing that these kids have significantly increased risk of brain injuries from their disease. Kids who are tested and found to have problems can be treated when young, and will have better outcomes if treated early instead of "caught late".
So, that's why at Children's of Minnesota we are trying to do "well child neuropsychological screening" for every child, every year, regardless whether or not the school or family is reporting any problems.
Karen E. Wills, Ph.D., LP, ABPP
Pediatric Neuropsychology
Department of Psychology
Children's Hospitals and Clinics
2525 Chicago Avenue South (mailcode 17-301)
Minneapolis, MN 55404
(612) 813-6344, (fax 612-813-8263)
karen.wills@childrensmn.org
Download the following resources in Microsoft Word format by clicking on the
hyperlinks beow
Advocate
letter to State Education Dept
Sickle Cell Educational
Implications
Other
Health Disability Criteria
Sickle Cell
Library Resources
Request
for a Case Study Evalustion
Sickle
Cell Disease flyer for PLANE Program for Learning Assessment and
Neuropsychological Evaluation
PLANE
update
Sickle Cell Disease Spreads to Latinos
The painful blood disorder called sickle-cell disease is striking an
increasing number of Latino people in Colorado, according to University of
Colorado researchers. The trend in the disease — long associated with
African-Americans — is worrying because many Latinos aren't as aware of the
risks, said Kathy Hassell, medical director of the university's Sickle Cell
Treatment and Research Center.
"Obstetricians have gotten pretty good at screening African-American
women, but they don't think about Ms. Lopez or Ms. Gonzales," Hassell said.
"There's no word in Spanish for sickle cell." Hassell has been
tracking the percentage of babies born every year with a single sickle-cell gene
— the disease occurs only in those who get a sickle-cell gene from both mother
and father.
The percentage of sickle-cell carriers who are Latino has jumped from 10
percent to 32 percent in the last 20 years — a time when the Latino population
in Colorado has more than doubled, according to U.S. census figures.The Sickle
Cell Center is beginning to print educational brochures in Spanish, and it's
making sure translators are available to counsel patients.
"This may be the tip of the iceberg," Hassell said. Sickle-cell
disease is named for the crescent-shaped red blood cells that mark the illness.
Normal red blood cells are smooth and round. Because those sickle red blood
cells don't carry oxygen effectively, people with the disease are often anemic.
The Colorado center identifies about 10 new cases a year among the state's
75,000 newborns. Sickle-cell patients are vulnerable to life-threatening
infections, may have strokes as children, often die in their 40s or 50s and have
intense "pain crises" requiring hospitalization.
Preventive measures — such as daily penicillin drops for babies — can
reduce the number of organ-damaging infections, triggered because the spleen
can't effectively filter sickled blood. "It used to be that 30 percent of
children died before (age) 5 of overwhelming infection," Hassell said.
"Now, every newborn in the state is screened, and we try to send a nurse to
the family's home for education." Thursday morning at The Children's
Hospital sickle center in Aurora, 19-month-old Adrian Perez-Vaoeriano sat
tearful on his mother's lap, taking shaky breaths as the two waited for
blood-test results.
A batch of donated red blood cells was a good match, so Adrian started his
seventh red- blood-cell transfusion — a monthly six-hour ritual he'll continue
until he's at least 2 years old. Soon after he turned 1, the left side of his
belly became rock-hard, said his mother, Leivi Vaoeriano. She rushed him to
Children's Hospital, where doctors used a transfusion to clear the sickle blood
clogged in his spleen, nurse coordinator Laura Cole said. "When he's 2,
they'll take out his spleen," Cole said. Adrian's mother said she was
baffled by her son's diagnosis, which she learned about when he was about 2
months old. "I just didn't know what it was," Vaoeriano said. Some of
her family members had heard of the disease, she said, but they had no idea that
Hispanic people got it. "Everyone was confused. They said: 'Why does he
have this? We're from Acapulco,' " Vaoeriano said.
To get sickle-cell disease, a person must inherit two mutated genes — one
from each parent, Hassell said. So if the gene is cropping up more often among
Latinos, it'll eventually mean more disease. "We know this is not just an
African-American disease," said Willarda Edwards, president of the Sickle
Cell Disease Association of America, in Baltimore. "I have people from
Nebraska calling me saying, 'I'm not black, but I got this.' Anyone can,"
Edwards said.
Reaching other races
Sickle-cell disease has long been associated with African- Americans,
but the gene is also common among people of Mediterranean and Indian descent,
Edwards said, and increasingly in Latino populations. The disease probably
evolved in parts of the world where malaria is or was a problem, Edwards said.
People with one sickle gene have some protection against malaria. Newborn
screens in every state now tell parents if their child is a carrier, but since
carrying the gene doesn't cause disease, parents may forget to inform their
children later on. When two people who each carry the gene have a child, the
chance is 25 percent that the baby will have sickle-cell disease.
http://www.denverpost.com/news/ci_8516076
Bitter pill: Prescription discrimination - Minorities
face pain-med bias
Whites remain much more likely than
nonwhites to receive narcotics for pain treatment at hospital emergency rooms,
new data shows, and Boston-area patients and physicians say the stubborn
disparity leaves minorities in prolonged discomfort and can alienate them from
the health-care system.
“I find that every time I go in the ER I’m rolling the dice,” said
Magalie Jean-Michel, spokeswoman for the Greater Boston Sickle Cell Disease
Association, whose son Rashard, 14, suffers from the painful blood disorder.
“All I ask is that they give my son some type of painkiller until they get
test results back or a doctor’s approval for something stronger,” she said.
“There are physicians and nurses that are very attentive, personable and not
judgmental with treatment. But I do come across individuals I feel should not be
working in the ER.”
Narcotic-based pain treatment has risen nationally in recent years - a
worrisome issue for many medical professionals - but that increase has not
reduced the racial and ethnic disparities in prescribing medicine, according to
a January study in the Journal of the American Medical Association.
The study’s analysis of a government survey of at least 15,000 emergency
room visits in a span of 13 years at 500 hospitals nationwide showed that pain
affliction accounted for 42 percent of visits. Opioid prescribing for
pain-related visits increased from 23 percent in 1993 to 37 percent in 2005.
According to JAMA, white patients with pain were likely to receive an opioid
31 percent of the time, blacks 23 percent of the time. Twenty-four percent of
Hispanics were prescribed opioids; other racial groups including Asians were
at 28 percent.
“While quality pain-care improvement is a good thing overall, it
doesn’t necesarily improve racial disparities in care,” said Dr. Alexander
Green, senior faculty member at the Disparity Solution Center in the Institute
of Health Policy at Massachusetts General Hospital.“These disparities exist
much more broadly,” said Green. “Often, minority patients do feel they are
being treated unfairly for a number of different reasons. While doctors feel
they are trying to do their best, studies show they are providing a different
level of care without knowing it.”
Green said some medical professionals may believe minority patients are
improperly seeking drugs because of unconscious biases and media messages.
“It’s not a matter of intentional racism,” said medical ethicist Dr.
Mildred Solomon of Harvard Medical School. “I think most health-care
providers deeply want to help people of all races, but there are an enormous
number of barriers.”
Other factors contributing to the disparity may include cultural
differences, human variation, or miscommunication between patients and medical
professionals. Patients’ expectations of care or an underrecognition of pain
also may play a role as to why racial disparity is a problem in hosptial
emergency treatment. “There’s an interpretation and communication that
goes on between a patient and doctor,” said Solomon. “If that’s not
perfectly aligned, the physican might miss what it is that the patient is
trying to communicate, not because they are racist but because they may not be
as attuned to what the patient is saying.”
Green said more guidelines for treating conditions in the ER may curb
disparities. “Having to wait long amounts of time, being treated
disrespectfully, lack of explanations from doctors - these are anecdotes that
we hear,” he said. “Even though it’s not clear whether these are only
perceptions or reality, studies show they may be true.”
http://news.bostonherald.com/news/regional/general/view.bg?articleid=1078890&srvc=home&position=also
New Stem Cell Technique Improves Genetic
Alteration
ScienceDaily (Mar. 9, 2008) — UC
Irvine researchers have discovered a dramatically improved method for
genetically manipulating human embryonic stem cells, making it easier for
scientists to study and potentially treat thousands of disorders ranging from
Huntington’s disease to muscular dystrophy and diabetes.
http://www.sciencedaily.com/releases/2008/03/080307150657.htm
UT Southwestern researchers investigate
predictors for sickle-cell-anemia complications
DALLAS – Feb. 29, 2008 – Researchers at UT Southwestern Medical Center
have determined that the level, or saturation, of oxygen in blood could be used
to identify children with sickle cell anemia who are at an increased risk of
stroke.In a related study, they have also found that a published method used to
predict severe complications of the disease may not be adequate.
“Stroke is a serious but increasingly preventable complication of sickle
cell disease,” said Dr. Charles Quinn, assistant professor of pediatrics at UT
Southwestern and lead author of a study appearing in February’s British
Journal of Haematology. “Several factors have been identified that
increase risk for stroke, but better screening tools are still
needed.”Hemoglobin is an oxygen-transport protein in red blood cells. People
with sickle cell disease, including an estimated 100,000 Americans, have a
genetic error affecting their hemoglobin. The defect turns normally soft, round
blood cells into inflexible, sickle-shaped cells. The altered shape causes
blockages in blood vessels and prevents body tissues from receiving oxygen.
The researchers reviewed the cases of 412 children who are part of the Dallas
Newborn Cohort, the world’s largest group of patients with sickle cell disease
who were initially diagnosed by newborn screening. All patients reviewed were
born after Jan. 1, 1990, a date chosen because patient data was available
electronically.Oxygen saturation in the children’s blood was tracked over
time, and the records of those who suffered a stroke were compared to those who
did not. The children who had lower levels of oxygen in their blood were more
likely to develop stroke, the researchers found.
“A decline in oxygen saturation over time seems to further increase the
risk of stroke,” said Dr. Quinn. “Oxygen saturation is easily measured,
potentially modifiable and might be used to identify children with sickle cell
disease who are at greater risk of having a stroke.”
http://www.eurekalert.org/pub_releases/2008-02/usmc-usr022708.php
Creating a Cord-Blood Lifeline
The decision to donate a newborn's umbilical-cord blood is, for many
expectant mothers, a simple checkmark on a long list of prenatal choices. But
for Noel Beninati, one donor's checkmark offered a lifeline. Last May, Beninati
received a transplant of stem cells harvested from the blood of an infant's
discarded umbilical cord at Boston's Dana Farber Institute, to help him fight a
rare blood condition called myelodysplastic syndrome. After doctors couldn't
find a matching bone-marrow donor, the 58-year-old New Yorker says his last hope
was cord blood, a solution that would not exist without parental donors. New
parents, Beninati urges, "must understand the importance this decision can
mean for the public good."
State legislators agree. More and more have introduced or passed laws to
mandate that doctors and hospitals educate expectant parents about the
possibility of cord-blood donation. Doctors can now treat some 70 diseases using
stem cells harvested from cord blood, and states including Oklahoma, Michigan
and Arkansas are considering bills to fund the establishment of additional local
public cord-blood banks and collection centers. "Ideally, we want people to
see this as a public service akin to blood or organ donation," says
Oklahoma state senator Jay Paul Gumm, who has sponsored such legislation.
"Something that they automatically think to sign up for."
http://www.time.com/time/health/article/0,8599,1717283,00.html
Sickle Cell Disease in Nigeria
Sickle cell anemia is one ailment that is affecting a large
percentage of Nigeria’s population, and due to the high cost of treatment,
many find it difficult to manage. A non-governmental organization (NGO), Elewura
Sickle Cell Centre, based in Ibadan, the Oyo State capital and the United
Kingdom, has however come to the rescue of sickle cell patients who can’t
afford the cost of treatment.
Elewura Sickle Cell Centre is an organisation that caters
for sickle cell patients who can not afford to pay for their drugs. Aside from
assisting patients with drugs, the organization puts in place sensitization programmers
to enlighten people about the sickle cell anemia, while also providing
pre-marital counseling to intending couples.
http://www.tribune.com.ng/27022008/features.html
February 2008
New Sickle Cell Day Hospital Unit in New Orleans
http://include.nurse.com/apps/pbcs.dll/article?AID=/20080211/ED02/302120038
In post-Katrina New Orleans, a lack of primary care physicians means that it can
often take up to a month to get a doctor’s appointment. As a result, many of
the city’s sickle cell patients have been coming to the emergency rooms
seeking treatment. Kruse-Jarres said that in the EDs, few doctors and nurses
have specialized training or knowledge in the treatment of sickle cell. The new
Tulane day hospital will meet a need by offering a place where patients can get
regular care and treatment from a staff that specializes in the disease.
The day hospital has five beds and a full-time staff consisting of a nurse, a
nurse practitioner and a social worker. Open during the daytime hours to those
over the age of 18, the hospital works with patients to create a
multi-disciplinary program of care and can treat patients when the pain gets out
of control. A social worker will also work with the hospital to help patients
manage the pain and to help them secure insurance or coverage for medical bills.
“We’re not just treating pain as everyone does and letting that be the end
of the story. We’re trying to understand the pain, the different types and how
they have to be treated. The social worker will be in once a day to do
assessments on the patients. We’ve really incorporated the psychological
aspects of pain management,” said Kruse-Jarres.
She also said that the sickle cell day hospital will work in conjunction with
personnel in the emergency room to develop guidelines for seeing and admitting
sickle cell patients.
The hospital is being subsidized by a $420,000 grant from Baptist Community
Ministries that will cover the nurse practitioner and social worker for three
years. Tulane offered space and a nurse to the program. The idea for a sickle
cell day hospital was based on the sickle cell clinic at Montefiore Medical
Center in New York. The Adult Bronx Comprehensive Sickle Cell Center there has
been a national leader in treatment and research on the disease.
Every time patients go to the emergency room they see different doctors but at
the Tulane day hospital they will now be able to see the same practitioners.
Dana Sylvester, RN, who is staffing the hospital, said that she has seen the
trouble with sickle cell treatment first hand through the eyes of a good friend.
Johns Hopkins Opens Day Hospital - Center To Treat Severe Sickle Cell Pain
http://www.webwire.com/ViewPressRel.asp?aId=58097
http://www.hopkinsmedicine.org/Press_releases/2008/01_30_08.html
A new urgent care center specifically geared to treat sickle cell patients experiencing acute pain will open Feb. 5, physicians at Johns Hopkins Medicine announced. A formal opening celebration is scheduled for Feb. 18.
Johns Hopkins opened an adult sickle cell Center in 2000 to provide chronic care for patients, but the new center fills a serious treatment gap for patients with pain too severe and too sudden to wait for care. Most head for crowded emergency rooms, where there may be long delays in getting infusions of powerful narcotics to stop the pain.
Sickle cell anemia, an inherited disorder that affects mostly people of African and Hispanic heritage, is named for the crescent- or sickle-shaped blood cells caused by the disease. The C-shaped cells periodically clump inside blood vessels, blocking circulation and causing severe anemia, increased risk of infections or strokes, and episodes of extreme pain that can last hours or days. These episodes are so severe that physicians refer to them as a “sickle cell crisis.”
“Emergency departments are crowded and busy, making it difficult for patients to get the medications they need,” says Sophie Lanzkron, M.D., assistant professor of medicine and oncology and director of both the new center and ongoing adult program. “Frequent trips to request powerful narcotics also often wrongly stigmatize sickle cell patients as drug addicts who need a quick fix, so lots of patients stay home and suffer because the thought of going to the emergency room is so uncomfortable,” Lanzkron adds.
The new urgent care center, known as they Sickle Cell Infusion Center, scheduled to operate Monday through Friday 8:30 a.m. to 5 p.m., was championed and designed by both medical experts and community leaders familiar with the burdens carried by sickle cell patients.
Myron L. Weisfeldt, M.D., physician in chief and chairman of the Department of Medicine at Johns Hopkins, worked with Lanzkron and other Johns Hopkins faculty and staff to develop the center and obtain financial support. The team secured funding from Priority Partners and Amerigroup, managed care organizations that provide medical assistance to low-income individuals. Priority Partners is partially owned by Johns Hopkins HealthCare.
These insurers will pay a set fee to the urgent care center each month to enroll their members into programs that include unlimited visits. “Paying for acute treatment in advance not only helps patients, but saves money overall by reducing costly visits to emergency rooms,” Lanzkron says.
In an average month, the emergency room at The Johns Hopkins Hospital gets about 50 to 70 visits from sickle cell patients. Though the urgent care center will be open only during business hours, Lanzkron expects that it will absorb the bulk of patient visits to treat sickle cell crises.
Last week to Vote for your favorite Children's Hospital
http://www.colgate.com/app/Colgate/US/Corp/CommunityPrograms/show-the-love.cvsp
Colgate-Palmolive and Starlight Starbright
Children’s Foundation have teamed up this year to help children with Sickle
Cell Disease and their families cope with the pain, fear and isolation of this
terrible disease. By providing FUN CENTERS in hospitals, these children can
forget about their illnesses for a moment and remember how to have fun.
We asked you to “Show the Love” by voting for a
hospital to receive a Fun Center. The outpouring of support has been wonderful,
and Colgate-Palmolive is awarding all nine participating hospitals a Fun Center!
And now you can make an even bigger difference. Voting remains open through
February 29, and the hospital that receives the most support will receive an
additional Fun Center!
January 2008
Thank you for Responding
Last month, the National Heart, Lung and Blood Institute of the NIH issued a “Request for Information”
(RFI) that seeks broad input about research priorities in Sickle Cell Disease (SCD). This RFI provides a unique and important opportunity for the SCD community to advocate for basic and clinical research to improve treatments and health outcomes for those with the disease.
The attached “Joint Response from Members of the Sickle Cell Disease Community” printed below represents an effort to facilitate a strong response to this RFI by providing, in one document, a comprehensive overview of the many promising research opportunities in SCD that should be pursued during the next 5-10 years. The document was authored by the leadership of the Clinical Trials Consortium of the Comprehensive Sickle Cell Centers, the SCD Clinical Research Network, the recent SCD Workshop of American Society of Hematology, and the SCD Summit of the American Society of Pediatric Hematology Oncology - with broad input from many members of the SCD community.
JOINT response from MEMBERS OF THE Sickle cell disease community
to Defining a Research Agenda for Sickle Cell Disease and Other Hemoglobinopathies
Request for Information NOT-HL-08-108 (Receipt Date January 14, 2008)
Sickle cell disease (SCD) research has entered an exciting new era, filled with opportunity and promise. Three decades of basic and clinical research – much of it funded by the National Heart Lung and Blood Institute
(NHLBI) through the Comprehensive Sickle Cell Centers (CSCC) Program and other mechanisms – have expanded the pathophysiological model of SCD beyond polymerization of Hb S to include an in-depth understanding of the pathological behaviors of sickle cells and their protean effects on other cells and organs. SCD is now appreciated as a systemic disorder characterized by a complex vasculopathy that affects multiple organ systems. Enhanced understanding of the systems biology of SCD will continue to provide a variety of new targets for potential therapeutic intervention. Opportunities have never been greater to improve health outcomes and quality of life for the ~100,000 Americans with SCD and millions worldwide.
In 2007, NHLBI completed a strategic plan that will guide its research and training programs over the next 5-10 years (Appendix A). In recent years, several conferences and working groups have reviewed scientific advances in SCD, identified barriers to progress, considered and ranked research priorities, and made recommendations for pursuing those opportunities. Brief summaries of the 2003 NIH conference “New Directions for Sickle Cell Therapy in the Genome Era”, the 2006 NHLBI Level 1 Strategic Planning Working Group on Acquired and Inherited Blood Diseases, the 2007 American Society of Hematology Workshop on SCD, and the 2007 American Society of Pediatric Hematology/Oncology SCD Summit are attached. (Appendix B) While a range of opinions exists about the relative importance of specific scientific opportunities, these different groups have generated a remarkably consistent set of broad research priorities and recommendations that are tightly aligned with the 2007 NHLBI Strategic Plan. A synthesis of these deliberations is presented below and offered as a joint response to the current NHLBI SCD RFI (NOT-HL-08-108) from a variety of groups and individuals concerned about sickle cell disease. (Appendix C)
SCIENTIFIC PRIORITIES AND RESEARCH AGENDA
The SCD community shares great enthusiasm and a strong sense of urgency for pursuing the following opportunities to improve treatment, health outcomes, and quality of life for persons with SCD. These five interdependent and synergistic opportunities are equally important.
· To develop and expand curative therapies such as hematopoietic cell transplantation and gene therapy. Hematopoietic cell transplantation is the only curative therapy for SCD currently available, but its utilization is limited by the associated risks and the availability of suitable donors. Gene therapy also offers the promise of cure, but issues of safety, vector design, stem cell transduction, and clinical efficacy are yet to be resolved. Thus additional research is necessary to overcome biological, clinical and social barriers to these promising approaches. Basic research in immunology, stem cell biology, gene transfer,
hematopoiesis, and regulation of gene expression, as well as translational, clinical and outcomes studies, promise to broaden the application of these curative therapies to more individuals with SCD and prior to the development of irreversible organ damage
(NHLBI Strategic Plan, Challenges 1.1, 1.2). Because of the risks associated with these approaches, they will likely be reserved in the foreseeable future for patients with high morbidity and mortality risks. Thus, improved risk assessment strategies are needed, and other lower-risk therapies must be developed in parallel. (Challenges 2.2, 2.3)
· To elucidate the genetic modifiers of SCD and to integrate genetic information with biomarker, clinical and psychosocial data to improve risk assessment, to anticipate organ-specific morbidities, and to predict response to specific therapies. SCD is characterized by enormous phenotypic variability, so identification of modifier genes is clinically and scientifically crucial. To this end, robust genome-wide association studies are needed in a population well-characterized by phenotype, along with targeted genotype-phenotype correlations and physiological studies to define the mechanistic basis by which specific genes modify phenotype. Longitudinal studies will be essential to document the occurrence and progression of organ-specific complications. Risk stratification is particularly important since phenotypic diversity in SCD requires that high risk therapies be restricted to individuals with severe phenotypes and that therapies directed at the prevention of specific complications initially be tested and subsequently targeted to those at risk for those morbidities. Psychological, social, and economic factors are major determinants of health outcomes in other disorders, and their contributions to disease severity, health care access and utilization, and health outcomes in SCD should be investigated. As emphasized by the 2003 NIH SCD-Genome Conference (Appendix B), SCD is an ideal prototype for developing the clinical infrastructure and genetic,
physio-logical and statistical methodologies to pursue this endeavor in the genome era. (Challenges 1.2, 2.2, 2.3, 3.1, 3.2)
· To expand and integrate basic knowledge of hematopoiesis and gene regulation, sickle red cell
pathophysiology, vascular biology, inflammatory mechanisms, and coagulation regulation to refine the systems-biology model of SCD. An expanded, sustainable, multidisciplinary basic science research effort focused on SCD is crucial to generate novel treatment strategies for future clinical research. Increased expression of gamma globin mitigates severity of SCD, and achieving even higher levels of Hb F has the potential for far greater benefit. Better understanding of how the single amino acid substitution in Hb S leads to cellular and membrane abnormalities that trigger red cell dehydration,
hemolysis, increased adhesion, procoagulant activity, inflammation, and endothelial cell dysfunction will continue to provide new targets for therapeutic intervention (Challenge 1.1, 1.2). Greater insight into the mechanisms responsible for progressive damage to brain, kidney, lung, heart, bone, and other organs will advance prevention and treatment of organ-specific SCD complications. Furthermore, emerging genetic information will fuel basic research to delineate the molecular mechanisms responsible for phenotypic variation, both expanding our understanding of SCD and other vasculopathies and generating new therapeutic strategies to be tested in clinical trials. (Challenge 2.1)
· To develop evidence-based treatment strategies based on improved understanding of pathophysiological mechanisms, genetic modifiers, biomarkers, and environmental factors. Individual and combination therapies will be needed to prevent and better treat acute complications (e.g. pain, acute chest syndrome); to predict and preempt the development of specific organ damage and dysfunction; and to prolong and improve quality of life (Challenges 1.2, 2.1, 2.2, 2.3). A pressing need exists to compare known treatments (e.g. chronic transfusion,
hydroxyurea) and to systematically test new therapies in risk-stratified subpopulations. Unique opportunities also exist to adapt pharmacological therapies developed in other disorders that target disease mechanisms now known to contribute to SCD. For example, a variety of agents might target the inflammatory, adhesive, and/or procoagulant mechanisms at play in SCD. The development of novel strategies to treat and prevent organ damage and innovative approaches to long unsolved problems, such as pain, will require new collaborations with investigators in other disciplines. Quality of life measures and psychosocial interventions and outcomes will be important to the design of clinical trials and the subsequent applicability of the results to clinical practice. Consumer and community input will be critical to identify outcome measures most important to patients, and to ensure transparency, public awareness, and support of research efforts. (Challenges 3.1, 3.2, 3.3)
· To translate research advances into clinical practice, by developing and implementing evidence-based guidelines for medical and psychosocial SCD treatments and disseminating these therapeutic advances effectively into medical practice. This effort will depend not only on the development of new evidence-based treatments, but also on a better understanding of barriers to the delivery of appropriate care, especially for adults. Evidence that new treatments such as hydroxyurea are underutilized illustrates the significance of such barriers. Investigation of the social, cultural, and economic factors that prevent people with SCD from receiving appropriate health care is critically needed if treatments discovered in laboratories and developed in clinical trials are to benefit patients, especially those beyond the reach of academic medical centers. Collaboration with other specialists, emergency and primary care providers, and community-based organizations will facilitate effective communication of research advances and delivery of improved treatments to the public. (Challenges, 3.1, 3.3)
RECOMMMENDATIONS FOR ADVANCING THE RESEARCH AGENDA
To effectively address these scientific priorities, NIH should develop and support a Comprehensive SCD Research Program that includes four distinct but highly interactive components:
· Basic and Translational Research targeted to SCD is essential to expand knowledge of the pathophysiology of SCD, to provide the new scientific findings necessary to engender future therapies, and to attract and retain young investigators to the field. Synergistic, interactive research programs that incorporate both basic and translational studies could be encouraged through center and/or program-project initiatives and other mechanisms. Interaction between basic and clinical research efforts is crucially important to ensure smooth transition of scientific advances into clinical trials and to promote the translation of clinical research back to the laboratory. Basic and translational research programs also constitute an important resource of laboratory expertise and facilities to support a Clinical Trials Network, and should be involved in the early phases of clinical trials development. Thus, NHLBI support for basic and translational research should include mechanisms to ensure the close association of basic science investigators with clinical programs and with the SCD Clinical Trials Network. Requests For Applications
(RFAs) that target specific research opportunities should continue to be used to focus effort in areas of highest priority, to ensure the most effective and vigorous investigator-initiated effort, and to attract investigators from other disciplines.
(NHLBI Strategic Plan, Strategies 1, 2, 4, 6, 7)
· A SCD Clinical Trials Network to provide an adequate number of subjects for the timely completion of investigator-initiated collaborative clinical trials in SCD. To conduct multiple clinical studies, especially phase III trials in both children and adults, it is likely that a patient population of 20,000 or more would be required initially, given the stratification of the population by such factors as genotype (SS vs. SC, etc), age, gender, ethnic background, complications (e.g., ~10% of SCD-SS patients with stroke), concurrent therapy, geographic locale, etc. Participation of individual centers in the Network should be based on demonstrated and sustained ability to contribute subjects and high quality data to collaborative SCD trials. Some trials may require and benefit from international collaboration. Once established, the Network could complete meritorious trials previously initiated by the CSCC Clinical Trials Consortium and the SCD Clinical Research Network and would support the development, prioritization and implementation of investigator-initiated epidemiologic and phase I, II and III trials. This Network also could be an efficient vehicle for important health services, psychosocial, and outcomes research. An efficient and accountable Network infrastructure would require mechanisms to ensure appropriate prioritization and peer review of proposed protocols and scientific leadership of trials by the investigators that develop them. Collaborative support from other Institutes may be required to conduct the number of meritorious studies that will be needed during the next 5-10 years to move basic and translational observations through phase I, II and III trials and to develop evidence-based treatments. (Strategies 1, 3, 4, 5, 6, 7)
· A database of well-phenotyped patients coupled to a DNA repository is indispensable for pursuing genotype-phenotype correlations. Detailed data on carefully standardized and validated phenotypes should be collected longitudinally on a broadly-based SCD population. This database could serve as a resource to the Clinical Trials Network and permit risk stratification of study groups and genetic analysis of response to therapy. Current efforts to create such a DNA-linked database could be enhanced and expanded to realize this goal. Sustained funding dedicated to this priority will be needed and may require inter-Institute support. (Strategies 1, 2, 3, 4, 6)
· The training of new basic and clinical investigators is essential for any field, but the unique medical economics of SCD provides few resources to develop and sustain academic programs or to cultivate the careers of young investigators. The supply of SCD investigators – currently inadequate, especially in internal medicine – is likely to become even more critical in the near future. Basic and translational research programs and the Clinical Trials Network would provide ideal venues for training and career development. A variety of funding mechanisms (K01, K08, K23, Scholar Programs, and
CTSAs) and loan repayment programs could support this important need. In addition, the maintenance of a vibrant basic and clinical research program in SCD that offers the prospect of career advancement is absolutely crucial to encouraging young academicians to enter and remain in the field. (Strategy 7)
In addition to its primary mission to support scientific research and training, NHLBI has a critical interest in forming active partnerships with other federal government agencies* and with the SCD community to address three major barriers to advancing the research agenda in SCD: 1) the inadequate and poorly funded system of health care available for SCD patients, especially for adults; 2) lack of reimbursement by third party payers for “standard care” for SCD patients in clinical trials (in marked distinction to other disorders, such as cancer); and 3) absence of population-based information on the incidence, demographics, clinical spectrum, health care utilization, and outcomes of SCD. These barriers represent major health disparities that inhibit the design and implementation of clinical trials and the translation of research advances into clinical practice. NHLBI can play a key role in eliminating these barriers by partnering with other federal agencies* with the mission and potential resources to develop and implement strategies to improve access to and reimbursement for quality healthcare, including that provided through clinical
trials; to establish practice guidelines and standards of care; and to develop a population-based system of surveillance and outcomes tracking for SCD. (Strategies 3, 5, 6, 8)
*Health Resources and Services Administration (HRSA), Centers for Disease Control and Prevention (CDC), Agency for Health Research and Quality
(AHRQ), and Centers for Medicare and Medicaid Services (CMS).
APPENDIX A: 2007 NHLBI STATEGIC PLAN
GOALS AND CHALLENGES
Goal 1: To improve understanding of the molecular and physiologic basis of health and disease, and to use that understanding to develop improved approaches to disease diagnosis, treatment and prevention.
Challenge 1.1: To delineate mechanisms that relate molecular events to health and disease.
Challenge 1.2: To discover biomarkers that differentiate clinically relevant disease subtypes and that identify new molecular targets for application to prevention and diagnosis – including imaging, and therapy.
Goal 2: To improve understanding of the clinical mechanisms of disease and thereby enable better prevention, diagnosis and treatment.
Challenge 2.1: To accelerate the transition of basic research findings into clinical studies and trials and to promote the translation of clinical research findings back to the laboratory.
Challenge 2.2: To enable the early and accurate risk stratification and diagnosis of cardiovascular, lung, and blood disorders.
Challenge 2.3: To develop personalized preventive and therapeutic regimens for cardiovascular, lung, and blood disorders.
Goal 3: To generate an improved understanding of the processes involved in translating research into practice and use that understanding to enable improvements in public health and to stimulate further scientific discovery.
Challenge 3.1: To complement bench discoveries and clinical trial results with focused behavioral and social science research.
Challenge 3.2: To identify cost-effective approaches for prevention, diagnosis, and treatment.
Challenge 3.3: To promote the development and implementation of evidence-based guidelines in partnership with individuals, professional and patient communities, and health care systems and to communicate research advances effectively to the public.
STRATEGIES TO ADDRESS GOALS AND CHALLENGES
Strategy 1: Develop and facilitate access to scientific research resources.
Strategy 2: Develop new technologies, tools, and resources.
Strategy 3: Increase the return from NHLBI population-based and outcomes research.
Strategy 4: Establish and expand collaborative resources for clinical research.
Strategy 5: Extend the infrastructure for clinical research.
Strategy 6: Support the development of multidisciplinary teams.
Strategy 7: Develop and retain human capital.
Strategy 8: Bridge the gap between research and practice through knowledge networks.
APPENDIX B: CONSENSUS DEVELOPMENT ON SCD RESEARCH PRIORITIES, 2003 - 2007
In November, 2003, NIH hosted the conference “New Directions for Sickle Cell Therapy in the Genome Era” attended by 120 invited experts from the US and abroad. Specific research priorities identified included:
· Establish a “Multidisciplinary SCD Research Network with a central prospective registry of
well-phenotyped patients.”
· Increase in the number of basic, clinical, and social science researchers doing research on sickle cell disease.
· Studies of genetic markers, genotype/phenotype correlation and chemical genomics.
· Standardization of phenotype definitions.
In May, 2006, the NHLBI Level 1 Strategic Planning Working Group on Acquired and Inherited Blood Diseases identified six priorities that apply to sickle cell disease and other hemoglobin disorders:
· Training new investigators in non-malignant hematology.
· An expanded, coordinated and stable clinical trials system for blood diseases.
· Exploration of the source of human variation (genetic modifiers) in single gene disorders using SCD or thalassemia as models.
· Studying the interfaces between different biological systems by examining the interactions of
hematopoiesis, vascular biology, immunology, inflammatory states and iron metabolism.
· Understanding how genes interact with each other and are activated or silenced.
· Expansion of basic research in gene therapy, stem cell biology and transplantation, and small molecules.
In May 2007, the American Society of Hematology convened a Workshop on Sickle Cell Disease to assess the current state of research. Five research priorities were identified:
· Improve existing treatments, such as hydroxyurea and transfusion, and develop new therapies such as more effective reactivation of fetal hemoglobin, expanded use of stem cell transplantation, gene therapy, and modula-tion of other pathophysiological processes including adhesion, inflammation, coagulation, and platelet activation.
· Use of genomic, phenotypic, biomarker, and clinical data to define risk strata for SCD complications.
· Improve pain management and quality of life.
· Better characterize the mechanisms and natural history of organ damage (renal, brain, lung, and heart) and develop new approaches to prevention, treatment and identification of those at highest risk.
· Expand international research, with studies of natural history of SCD, hydroxyurea use and other approaches in Africa; evaluation of traditional remedies; and increased collaboration with Western European SCD investigators.
Recommendations included:
· Development of a new infrastructure for translational and clinical research and continued and expanded support for basic science research.
· Development of a single Cooperative Clinical Trials Group to conduct clinical research in SCD.
· Increased collaboration by NIH with other federal agencies to improve the organization and funding of clinical care for people with SCD.
In June, 2007, the American Society of Pediatric Hematology/Oncology convened a Sickle Cell Disease Summit at which a diverse group of 65 healthcare providers, investigators, and representatives of federal agencies, professional and community-based organizations and members of the affected community met to review the current status of, and possible actions to address, the disparity between SCD and other disorders in terms of advocacy, healthcare, and research support. The Summit identified opportunities and actions to improve access to care, to develop population-based surveillance to measure outcomes, and to enhance the role of the community in advancing a broad SCD agenda. Specific recommendations for basic, translational, and health services research included:
· To encourage NHLBI to lead the coordination of research among various NIH Institutes and to solicit cooperation from other federal agencies to address a broader SCD agenda.
· To strengthen and facilitate basic science research in SCD.
· To establish a single broadly representative, efficient and cost-effective SCD clinical research network.
· To develop, disseminate and facilitate implementation of evidence-based best practices, including standardized transfusion practices.
· To engage the affected community and community-based organization in the development and completion of research.
APPENDIX C: ENDORSEMENTS
-Sickle Cell Disease Association of America
· American Academy of Pediatrics
· American Society of Pediatric Hematology/Oncology
· NHLBI Sickle Cell Disease Advisory Committee
· International Association of Sickle Cell Nurses and Physician Assistants
· Steering Committee of the Comprehensive Sickle Cell Centers
· Steering Committee of the Sickle Cell Disease Clinical Research Network
· Steering Committee of the Pediatric Hydroxyurea Phase III Clinical Trial (Baby HUG)
In addition, the American Society of Hematology has noted that the recommendations of the Joint Response are consistent with those of the ASH Workshop on Sickle Cell Disease, a copy of which has been submitted in response to the
RFI.
We hope that this Joint Response, along with the many other perspectives you have received, will be helpful as you consider new approaches to supporting a research agenda focused on the improvement of health outcomes and quality of life for those affected by SCD.
Sincerely,
Clint Joiner and Peter Lane
Pain Common With Sickle Cell Disease
Jan. 14, 2008 -- Pain is "the rule rather than exception" among
adults with sickle cell disease, researchers report. Sickle cell disease is an
inherited condition in which certain red blood cells become crescent-shaped (sickled).
That makes it hard for those cells to pass through narrow blood vessels, which
deprives tissue of oxygen and causes pain.
Experts at the University of Virginia and Virginia Commonwealth University
studied 232 people age 16 and older (average age: 32) with sickle cell
disease.For six months, the patients kept daily diaries about their sickle cell
pain. Those diaries show that:
- 29% of the patients reported sickle cell pain nearly every day.
- 54% reported pain on more than half of the days.
- Only 14% rarely reported pain.
- Average pain intensity was in the middle of the study's pain scale.
The patients often didn't go see a doctor about their sickle cell pain,
handling it at home instead."Our results are both surprising and
striking," write Virginia Commonwealth University's Wally Smith, MD, and
colleagues. "Pain in adults with sickle cell disease is far more prevalent
and severe than previous studies have portrayed, and it is mostly managed at
home."Smith's team concludes that sickle cell disease should be recognized
as a source of chronic pain. The study appears in the Annals of Internal
Medicine.
Smith, W. Annals of Internal Medicine, Jan. 15,
2008; vol 148: pp 94-101.
http://www.voanews.com/english/Science/2008-01-18-voa48.cfm
http://www.abcnews.go.com/Health/PainManagement/story?id=4151169&page=1
Sickle Cell Disease in Camaroon
Sickle cell disease (SCD) research is still a dream especially for those who are powerless in terms of making it a public health priority. In a country of about 18 Million individuals and 25 to 30% of heterozygous, it’s calculated that some 4.000 babies with SS disease might come to life each year in Cameroon (Central Africa) .Healthcare facilities still lack basic tools and competent personnel to tackling the suffering of thousands of survivors who are endangered by precarious and risky blood transfusion setting where and when they exist. Most of the individuals with the disease do not attend any hospital or healthcare facility; they have to PAY and sometimes BRIBE to receive any attention. Poverty and impoverishment of families due to the cost of medical attention and drugs that are not covered by any sort of public or private assistance, increases the burden of the suffering and total morbidity/mortality.
This makes it extremely difficult to:
Sensitize public opinion (conferences, media interventions)
Organize health education
Advocate for premarital screenings and counseling
Set research plans and projects that can be funded (no official data is available on the gene)
Carry out outdoor activities in remote areas
Screen newborns and start early prophylaxis
Assure a good follow-up and control of complications…
There is no Comprehensive Sickle Cell Center (CSCC) and the promotion of quality of life for our patients can benefit from no facilities. Ignorance is still an additional cause of poor health and precocious onset of complications in our patients.
This type of situations can be managed within a well organized, financed and specialized sickle cell clinic.
There are still millions of persons with the disease throughout the world and every year, hundred thousands of newborns with the disease, come to life. In addition to preventing the spread of the gene which is vital and priority, research shall also look at molecules protecting from malaria and anemia, which appear to be some major causes with VOC, of admissions and deaths. Research priorities in Sickle Cell Disease (SCD) in our context could be traduced in terms of provision of basic treatments, training for dedicated personnel, and promotion of epidemiologic and clinical research to enable prevention, sensitization, and communication to eradicate the gene. Empowerment of communities shall be also considered.
I am a health care provider (Clinical Psychologist, PhD); researcher (bio-psycho-social determinants of morbidity and mortality in SCD focusing on depression as a clinical revelator); also advocate as I perform at least
6 conferences every year since 2006 in Douala on this subject matter; I also appear along with the sickle cell patients association, on radio or TV programs whenever the opportunity is offered to us.
I belong to an informal scd team at Laquintinie Hospital in Douala ( Douala has·3 Millions inhabitants and is the most populous town in Cameroon ). Our team is made of a Pediatrician, a generalist and I (Psychopathologist and Clinical Psychologist) who try benevolently to offer a clinical attention to hundreds of patients and parents, who would have otherwise, no particular place to go with their problems.
I was granted an observership in 2004 at the University of Miami School of Medicine, Division of Pediatric Hematology/Oncology attended their sickle cell clinics and experienced their sickle cell center. I then had a valuable understanding of the concept of a Comprehensive sickle cell center and dream of having at least one in Cameroon. My research on SCD and my PhD dissertation can show that a huge amount a suffering in scd patients are peripheral to the condition itself and can be reduced or suppressed with the type of commitment that is shown in the past programs and the present
RFI.
Dr Erero F. Njiengwé
Clinical Psychopathologist
Senior Lecturer - University of Douala
CAMEROON njiengwe@YAHOO.COM
Racial gap in ER opioid use still
persists
US hospitals are more likely to give painkillers to white patients than other ethnic groups despite studies in the 1990s that highlighted the problem, according to a study
During 1993-2005, there was a steady increase in the use of opioid painkillers to help emergency room patients complaining of pain, according to the study of nearly 375,000 hospital visits by a team of researchers led by Mark Pletcher of the University of California-San Francisco.
At the beginning of the period, only 23 percent of all patients visiting the hospital for pain were given opioids, said the study published by the Journal of the American Medical Association.At the end of the period, 37 percent were medicated with
opioids.However, there was a consistent difference between how often whites received the painkillers and how often African-Americans and Hispanics received them.
On average during the 13 years, 31 percent of whites were given opioids, while only 24 percent of Hispanics and 23 percent of blacks got them. For Asians and others, the rate was 28 percent.
And despite the overall rise in administering opioids over the period, the racial gap remained consistent at the end: in 2005, opioid prescription rates were 40 percent for whites, and 32 percent for all other ethnic groups.
For example, a white person going to a hospital emergency room in Los Angeles with a major arm or leg bone fracture was twice as likely to receive an opioid painkiller as a Hispanic with the same injury, the study said.While the study pointed out that the problem remains despite 1990s studies that showed the same phenomenon and the 1995 issuance of improvement guidelines for the treatment of acute and cancer pain, it could not fully explain the treatment discrepancy.
"Causes of disparities in medical care ... are complex, and simple racial/ethnic bias is unlikely to fully explain the problem," the study said.
http://www.sciam.com/article.cfm?id=racial-gap-in-er-opioid-u
Model Policy for the Use of Controlled
Substances
for the Treatment of Pain Federation of State
Medical Boards of the United States, Inc. Available
at http://www.fsmb.org/pdf/2004_grpol_Controlled_Substances.pdf
Rising teen star with sickle cell disease-
Dexter Darden plays the role of a tormented computer geek who gets the last
laugh in the original Disney Channel movie "Minutemen" airing at 8
tonight.
His movie debut is proof that the 16-year-old boy isn't letting a potentially
life-threatening disease or even a well-intentioned mother derail his longtime
dream of becoming a movie star. And the Disney Channel movie is a convincing
start for Darden, who has sickle cell anemia, an inherited blood disorder that
causes chronic pain by clogging blood vessels, which is damaging to tissues and
vital organs.
"I'm actually really excited," said Darden, who lives in the
township's Sicklerville section. "I'm psyched. I can't wait till it comes
out." Pat Darden wants her son to be a lawyer or doctor, but she's proud of
his successes. "I had a lot of faith in him. He's motivated. He always
wanted to do something in the arts. He sings. He dances. He acts. And I was
hopeful some doors would open for him and they did," she said.
Darden admits that he can see himself working as a pediatrician some day
because of his empathy for sick children. But for now, he's capitalizing on his
artistic talent and acting is at the forefront. Darden auditioned for the role
in New York City last summer. He wore his tube socks high, taped-up glasses,
old-fashioned basketball shorts and Converse in an attempt to appear
"over-the-top" geeky. The next day he was offered a role as Chester,
king of The Geek Squad. The movie was shot in Salt Lake City.
Darden will be watching the movie today at a private location in Margate. His
manager, Sabina Kolfa, has arranged a private dinner for him and his family,
friends and other talent agents. http://www.courierpostonline.com/apps/pbcs.dll/article?AID=/20080125/NEWS01/801250376/1006/NEWS01
December 2007
Request for
Information (RFI): Defining a Research Agenda for Sickle Cell Disease and Other
Hemoglobinopathies
This request for information (RFI) seeks comments on the current and evolving
scientific opportunities for investment in research that will lead to improved
understanding of sickle cell disease (SCD) and other hemoglobinopathies and
enable improved methods of treatment for the major clinical problems of those
affected with the diseases.
Background - The National Heart, Lung, and Blood
Institute (NHLBI) at the National Institutes of Health (NIH) has recently
completed a Strategic Plan that will guide the Institute’s research
investments in the areas of heart, lung, and blood diseases. The Institute
is now examining how it will address the goals defined in the Strategic Plan
across its broad research portfolio.
The mission of the NIH is to conduct and support research and research training.
The NHLBI is uniquely positioned to catalyze changes that transform new
scientific knowledge into measures that can improve the public health, and to
communicate advances in knowledge to the individuals and institutions directly
engaged in disease prevention and healthcare delivery. Research in the
field of SCD is supported by multiple Institutes at the NIH. The NHLBI
supports basic and clinical research in SCD and other hemoglobinopathies.
Over the past decade, several therapies (e.g., hydroxyurea, chronic transfusion,
and hematopoietic stem cell transplantation) have been developed that are known
to be effective in mitigating various complications of SCD. Many of them
have implications for other hemoglobinopathies as well. Earlier studies
supported by the NHLBI demonstrated the efficacy of prophylactic antibiotics for
prevention of early death in affected children. The results of those
studies led to widespread neonatal screening and greatly increased lifespans for
people born with SCD. We now seek input from the scientific community in
the major scientific opportunities in basic and clinical research for SCD, which
we aligned with the NHLBI Strategic Plan (http://apps.nhlbi.nih.gov/strategicplan/).
Information Requested - Please respond by
identifying what you consider to be the major scientific opportunities for
advancing understanding of SCD and other hemoglobinopathies, and providing
suggested approaches to best exploit them.
This RFI is for planning purposes only and should not be construed as a
solicitation for applications or as an obligation on the part of the Government
to provide support for any ideas identified in response to it. Please note
that the United States Government will not pay for the preparation of any
information submitted or for its use of that information. Responses will be
compiled and shared internally and with the National Heart, Lung, and Blood
Advisory Council, with one or more subcommittees of the Council, and with
scientific working groups convened by the NHLBI, as appropriate. In all
cases where responses are shared, the names of the respondents will be withheld.
We look forward to your input and hope that you will share this document with
your colleagues. Thank you very much for your help.
Responses- To respond, please link to the
online form at: http://www.nhlbi.nih.gov/funding/inits/sickle-cell-rfi.htm
Or send a letter, fax, or email to:
Request for Information: Defining a Research Agenda for Sickle Cell Disease and
Other Hemoglobinopathies
National Heart, Lung, and Blood Institute
Building 31, Room 5A48
9000 Rockville Pike
Bethesda, MD 20892- 2486
Fax: (301) 402-1124
Email: NHLBI_SickleCell@mail.nih.gov
On your response please provide the following (and include the Notice number
HL-08-108 in the subject line):
- Describe the scientific opportunities that are likely to have the greatest
effect upon the understanding of the biology of SCD and other
hemoglobinopathies in the next 5 to 10 years. In particular, please
identify the most important basic biologic questions that must be resolved
to enable development of new diagnostic and therapeutic targets.
- Describe the most important scientific opportunities for clinical research
on SCD and other hemoglobinopathies.
- Identify your relationship to research on SCD and other hemoglobinopathies
(i.e., are you a patient, a family member or close friend of a patient, a
member of an advocacy or community group, a basic researcher, a clinical
researcher, a health-care provider?).
Inquiries
Susan B. Shurin, M.D.
Deputy Director
National Heart, Lung, and Blood Institute
Building 31, Room 5A48
9000 Rockville Pike
Bethesda, MD 20892- 2486
Telephone: (301) 496-1078
Fax: (301) 402-0818
Email: Shurinsb@nhlbi.nih.gov
From: http://grants.nih.gov/grants/guide/notice-files/NOT-HL-08-108.html
The U.S. Senate passed S. 1858, the
Dodd-Hatch "Newborn Screening Saves Lives Act."
This bill includes provisions that, for
the first time, require annual funding for CDC's newborn screening quality
assurance program and that direct the Secretary of HHS to produce a contingency
plan for newborn screening operations -- both of which were recommended by
APHL. APHL is deeply appreciative of the work of Senators Christopher Dodd
(D-CT) and Orrin Hatch (R-UT)in advancing this important legislation, and we
look forward to working closely with Congresswoman Lucille Roybal-Allard (D-CA)
and Congressman Mike Simpson (R-ID) as they move their companion legislation,
H.R. 1634, through the House of Representatives.
Senators Chris Dodd (D-CT) and Orrin Hatch (R-UT)
applauded unanimous Senate passage of their legislation that will educate
parents and health care providers about newborn health screening, improve
follow-up care for infants with an illness detected through newborn screening,
and help states expand and improve their newborn screening programs.
“Investing in the health of our children is an
investment in the future of our country. Today, I am proud to say the
Senate passed legislation to protect the health of our most vulnerable citizens
– infants - by passing the Newborn Screening Saves Lives Act,” said Dodd.
“Incredible advances in medical technology have equipped us to better screen
and treat infants for congenital, genetic and metabolic disorders that, if left
untreated, could lead to severe disability or death. However, while some
newborn screening occurs in every state, fewer than half, including Connecticut,
actually test for the full recommended panel of 29 disorders. The bill
that passed today will provide resources for states to expand their newborn
screening programs. I thank my colleague Senator Hatch for joining
me in sponsoring this initiative, and I thank the rest of my colleagues in the
Senate for passing a measure that will help ensure that every newborn
child has the best possible opportunity to live a long, healthy and happy
life.”
“States will greatly benefit from federal guidance and
incentives to improve their newborn screening programs, and this bill authorizes
a modest amount of funding to help states expand and improve their programs,
provide much needed educational materials to families and improve follow-up care
and treatment of newborns that screen positive for a treatable condition,”
Hatch said. “It also helps to ensure the quality of laboratories involved in
newborn screening, so that tests are as accurate as possible and infants receive
appropriate care; and calls for a national contingency plan for newborn
screening for use in the event of a public health emergency. I greatly
appreciate my friend from Connecticut, Senator Dodd, for his leadership in
helping children.”
An estimated 4,000 babies are identified and treated
each year for conditions that could threaten their lives or health, often
preventing death and long-term disability. Unfortunately, parents are often
unaware that while nearly all babies born in the U.S. undergo some newborn
screening, the number and quality of tests vary from state to state. As a
result, a child with a given disorder will most likely receive successful
diagnosis and treatment if born in a state that tests for that disorder, but may
suffer irreversible injury or death if born in another state that does not
require such testing. Dodd and Hatch’s bill will provide grants and
incentives to states to help implement screening of the full panel of
disorders recommended by the Advisory Committee on Heritable Disorders in
Newborns and Children.
Senator Dodd has introduced this legislation in each
Congress beginning in 2002, and convened a hearing on the bill in June
2002 before the Senate’s Subcommittee on Children and Families. Senator
Hatch joined him as the lead cosponsor this year. “The Newborn
Screening Saves Lives Act” is endorsed by the March of Dimes and the
Association of Public Health Laboratories, among other organizations. To see the
Bill http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_bills&docid=f:s1858es.txt.pdf
UAB Researchers Say New Stem Cell
Technique Cures Sickle Cell in Mice
Researchers at UAB (University of Alabama at Birmingham), along with a team
from the Whitehead Institute, report successfully treating sickle cell anemia in
mouse models using induced pluripotent stem (iPS) cells, a new stem cell
technique that uses skin cells and does not require embryos. The findings,
published in Science Express Online on Dec. 6, are the first to actually use the
iPS technique to treat disease in an animal model.
The iPS technique received widespread attention in November when two
laboratories reported using the process to turn human skin cells into stem
cells, cells which can then be induced to form any other type of cell.
Scientists believe stem cells have great potential in treating a variety of
human diseases.
“The UAB/Whitehead teams took skin cells from mouse models genetically
engineered to have sickle cell disease and reprogrammed them into iPS cells by
adding four genes to each cell,” said Tim M. Townes, Ph.D., professor and
chair of the Department of Biochemistry and Molecular Genetics at UAB and
co-senior author of the study. “The new genes remodeled the chromosomes that
instruct a skin cell to be a skin cell, so that the cells revert to stem
cells.”
The researchers then used a DNA fragment engineered by Townes’ laboratory
in 2006 to correct the basic sickle mutation in the cells. The corrected iPS
cells were then induced to become blood stem cells (capable of making any type
of blood cell) and were transplanted back into the diseased mice.
“The new blood stem cells began to function properly, making normal red
blood cells that did not sickle,” Townes said. “The animals showed no
symptoms of the disease and did not reject the transplanted cells.”
Previous work with iPS cells showed simply that the process worked and skin
cells could be transformed into stem cells. Townes and colleague Rudolf Jaenisch,
Ph.D., with the Whitehead Institute and a professor of biology at MIT and
co-senior author of the study, say this “proof of principle” is the first
example of creating iPS cells derived from a disease model and using these cells
to correct a genetic mutation and treat a disease.
“These findings are a major step forward in developing a cure for sickle
cell anemia,” Townes said. “We anticipate that this therapy will work in
humans as it works in mice. And it cured sickle cell in mice.”
There are obstacles to be overcome. The added genes that transform regular
cells into iPS cells are delivered by retroviruses and there are inherent risks
in the use of retroviruses. The process also uses a cancer gene to stimulate
cell division – sort of like a starter for sourdough bread. That gene has to
be regulated, so it does not stimulate uncontrolled cell division, potentially
causing a risk for cancer. Townes says researchers are already at work in
resolving these issues, although it may be years before iPS is a viable approach
to treat disease in humans.
This research was funded by the National Heart, Lung and Blood Institute, one
of the National Institutes of Health (NIH). http://main.uab.edu/show.asp?durki=115591
http://www.phgfoundation.org/news/3935/
Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R. Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin.
Science. 2007 Dec 6; http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18063756&ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Children with Sickle Cell Disease and Silent Strokes Show
Some Relief with Blood Transfusion Therapy
A group of children who have sickle cell disease and who experience silent
strokes showed some relief from the silent strokes with blood transfusion
therapy, researchers at Washington University School of Medicine in St. Louis
have found. The study's results will appear in a future issue of Pediatric
Blood and Cancer but are available for review in its advance online
publication.
In a Phase II study of 10 children with sickle cell disease who also had
multiple silent strokes, or cerebral infarcts, the majority of families were
committed to having their children receive blood transfusions for two years,
showing that the therapy was feasible. In addition, the blood transfusion
therapy helped to shrink the lesions on the brain caused by the infarcts and
eliminated one lesion completely, said Allison A. King, M.D., a pediatric
hematologist at St. Louis Children's Hospital and a researcher at Washington
University School of Medicine. Lesions are small areas of damaged tissue thought
to be due to blockage of small arteries in the brain.
Silent strokes are strokes that don't show the classic symptoms of overt
strokes, such as numbness, tingling, headache or slurred speech. Blood
transfusion therapy has been shown to be effective in preventing overt strokes
in patients with sickle cell disease, but its effectiveness and the willingness
of families to participate in long-term treatment to prevent silent strokes had
not been tested.
Sickle cell disease is an inherited blood disorder affecting red blood cells
that contain hemoglobin, a substance that carries oxygen from the air in the
lungs to all parts of the body. In patients with this disease, red blood cells
contain an abnormal type of hemoglobin that causes the normally round, flexible
red blood cells to become sickle- or crescent-shaped. The sickle cells can't
pass through tiny blood vessels, preventing blood from reaching the body's
tissues, which can result in tissue and organ damage, pain and stroke.
Sickle cell disease affects about 70,000 people in the United States. It
occurs in about 1 of every 500 African-American births and 1 of every 1,000 to
1,400 Hispanic-American births. While there is no cure for the disease, blood
transfusions and bone marrow transplants have been shown to be effective
treatments by replacing short-lived sickle cells with longer-lived healthy red
blood cells, although bone marrow transplants have a 10 percent mortality rate
because of the possibility of rejecting the bone marrow, complications such as
seizures and a high risk of infection.
In the study, brain lesions in six patients shrank after two years of regular
blood transfusions, and no new silent strokes occurred. One patient had a lesion
disappear, however, that patient did not continue with further blood
transfusions, and the lesion returned at more than three times its original
size, suggesting the need for prolonged transfusions. A lesion grew larger in
the seventh patient.
Many of the lesions occur in the frontal lobe of the brain, which controls
the cognitive function or problem-solving area, or in the occipital lobe, which
controls the visual processing center, King said. Neuroradiologists can locate
the lesions using magnetic resonance imaging (MRI).
"Because these lesions are usually in the frontal lobe, it is important
to do cognitive testing on these children to determine any impairment,"
King said. "We hope that by preventing further lesions through blood
transfusions that we can preserve their ability to think and learn."
A total of 71 percent of the school-aged children in the study were receiving
special education services and 57 percent had failed a grade in school. Previous
School of Medicine research shows that 80 percent of students with silent
strokes perform poorly in school.
King said the results of the trial were encouraging to health-care
professionals treating children with sickle cell disease.
"What we found in this trial is that families and children with sickle
cell disease and who experience silent strokes are willing to commit to blood
transfusion therapy for this condition," King said. "If these children
are left untreated, their risk for an overt stroke is very high, but if we use
blood transfusion therapy, they may have a lower risk for overt stroke and no
evidence of new silent infarcts on an MRI."
Results of this Phase II trial spearheaded a larger, Phase III study that is
evaluating 1,800 children in the United States, Canada and Europe. That trial,
called the Silent Cerebral Infarct Multi-Center Clinical Trial, is headed by
Michael R. DeBaun, M.D., professor of pediatrics at the School of Medicine.
Through it, researchers will further determine the effectiveness of blood
transfusion therapy to prevent silent strokes in children with sickle cell
disease and to prevent further cerebral injury. http://www.newswise.com/articles/view/536080/
IMPACTS Trial Uderway
Anthera Pharmaceuticals, Inc., a privately held
biopharmaceutical company developing anti-inflammatory drugs, announced today
that the U.S. Food and Drug Administration (FDA) Office of Orphan Product
Development has granted A-001 orphan drug status for the prevention of acute
chest syndrome in patients with sickle cell disease. A-001 is currently being
evaluated for acute chest syndrome in a Phase II clinical trial in the United
States called IMPACTS (Investigation of the Modulation of Phospholipase in Acute
ChesT Syndrome).
In addition to orphan drug designation, the FDA has granted
Anthera expanded enrollment of the IMPACTS trial to patients as young as five
years of age. "The orphan drug designation signifies an important milestone
for Anthera in the development of A-001," stated James E. Pennington, M.D.,
Executive Vice President and Chief Medical Officer at Anthera Pharmaceuticals,
Inc. "Orphan drug designation, in addition to our recent fast track
designation from the FDA, further strengthens our development program and allows
us to accelerate our efforts to develop a new treatment for this devastating
condition, for which there is no cure." About Acute Chest Syndrome Acute
Chest Syndrome (ACS) primarily affects children suffering from sickle cell
disease. It is believed that the incidence of sickle cell disease is highest in
children two to four years of age decreasing gradually to its lowest value in
adults. Patients five to eleven are also a large part of the population who
could benefit from a new therapy. ACS is also believed to be a contributor to
pulmonary function abnormalities, pulmonary hypertension, and long-term
mortality.
About the IMPACTS trial The IMPACTS trial began recruiting
patients in January 2007 and is a double-blind, randomized, parallel group,
placebo-controlled dose escalation study aimed at preventing a severe
respiratory complication of sickle cell disease, acute chest syndrome. Acute
chest syndrome is a form of acute lung injury and is the leading cause of death
in sickle cell disease patients. It commonly follows admission to the hospital
for other reasons, especially an episode of bone pain (a prominent feature of
sickle cell disease). Recent academic clinical studies have demonstrated that
serum secretory phospholipase A2 (sPLA2) levels rise in advance of acute chest
syndrome, and therefore help identify patients at-risk. This creates a unique
opportunity for early intervention for a serious inflammatory lung disease with
a potent inhibitor of sPLA2 such as A-001. Worldwide, nearly 200,000 suffer from
some form of sickle cell disease. It accounts for an estimated 60,000
hospitalizations per year and significantly reduces life expectancy.
"Current treatment options are limited for even the common complications of
sickle cell disease. As such, discovery of sPLA2 as a potential therapeutic
target for patients at risk for acute chest syndrome has opened new prevention
and treatment opportunities," says Clark Brown, M.D., Ph.D., IMPACTS
investigator at Emory University, and a physician at the Aflac Cancer Center and
Blood Disorders Service of Children's Healthcare of Atlanta. "The IMPACTS
study represents a promising step forward in the care of patients with sickle
cell disease." Further information about this clinical trial, sickle cell
disease, and acute chest syndrome can be found at http://www.IMPACTStrial.com
Reports from 2007 ASH meeting:
ATLANTA, Dec. 8 /PRNewswire-USNewswire/ -- New research to be presented at
the 49th Annual Meeting of the American Society of Hematology in Atlanta, GA,
will provide important insight into the treatment and management of sickle cell
disease and thalassemia, both disorders of the red blood cells. Specifically,
data will be presented on advancements in iron chelation therapy, treatments
necessary for patients who require multiple blood transfusions because of the
risk of excess iron. Researchers will also unveil new findings about brain
damage in sickle cell patients, a complication of the disorder that can occur as
patients age. Additionally, retrospective and prospective trials among Florida
Medicaid populations and patients in Nigeria, an area with the highest global
burden of sickle cell disease, will show the need for physician education to
address the underutilization of hydroxyurea, which is an efficacious treatment
associated with a significant reduction in sickle cell complications,
hospitalizations, and transfusion requirements by about 50 percent and in
mortality by 40 percent. A press conference revealing this new research will
take place Saturday, December 8, from 1:30 p.m. to 2:30 p.m.
"Sickle cell disease, once considered a fatal pediatric condition, is
now a chronic adult illness. As physicians, we need to better understand how to
treat sickle cell patients from childhood through their adult life," said
press conference moderator Marilyn Telen, MD, Division Chief of Hematology, Duke
University, Durham, NC. "Further, by understanding how to effectively
mitigate the consequences of multiple transfusions, particularly iron overload,
we can better serve a broad range of patients who suffer from red blood cell
disorders."
-- Hydroxyurea, a highly efficacious treatment for sickle cell patients, is
underutilized in a Florida Medicaid population [Abstract #79]
Richard Lottenberg, MD, Division of Hematology/Oncology, University of
Florida College of Medicine, Gainesville, FL
This retrospective cohort study aimed to determine adoption and utilization
of hydroxyurea therapy in sickle cell disease among 2,301 Florida
Medicaid-eligible patients over 16 years of age. It found that the prevalence of
hydroxyurea use in this Medicaid population is low. Hydroxyurea adoption was
determined by the presence of at least one hydroxyurea pharmacy claim and about
17 percent of the patients had at least one pharmacy claim for hydroxyurea.
Hydroxyurea users compared to non-hydroxyurea users were more likely to be
males, older than 25, with a history of using slow-release opioid medications,
or receiving red cell transfusions. A substantial number of patients that met
FDA-approved criteria for hydroxyurea did not receive it. The study also found
that early therapy drop-out and low adherence rates were common in patients
prescribed hydroxyurea. These findings highlight the need to develop programs to
enhance physician adoption and prescribing of hydroxyurea, as well as
educational materials to increase patient adherence.
-- First-ever evaluation of hydroxyurea use in Nigerian population shows
absolute lack of use by physicians in area with highest incidence of sickle cell
disease worldwide [Abstract #80]
Zakari Aliyu, MD, MPH, Center for Sickle Cell Disease, Howard University,
Washington, DC
This prospective trial included interviews with 206 adult and pediatric
sickle cell patients and 10 hematologists, and reviewed data from more than
1,000 patients, all based in Nigeria, about hydroxyurea utilization. The study
found that 100 percent of the Nigerian hematologists surveyed reported
discomfort with instituting hydroxyurea as a treatment option for sickle cell
disease patients. Barriers to hydroxyurea utilization identified by physicians
included safety and toxicity profile (100 percent), patient compliance (100
percent), effective follow-up (100 percent), drug availability (100 percent),
affordability (100 percent), and concern for reactivation of latent tuberculosis
(50 percent), carcinogenesis (100 percent), and teratogenicity (associated with
birth defects) (100 percent).
No patient was currently on hydroxyurea treatment and only 5 percent of the
patients interviewed had been informed of or were aware of hydroxyurea.
Patient-related barriers to hydroxyurea included lack of awareness (95 percent),
cost (100 percent), availability (100 percent), need for frequent follow-up (90
percent), risk of infections (98 percent), and pregnancy restrictions and need
for concurrent contraceptive use (98 percent).
The authors concluded that the absolute lack of hydroxyurea utilization in a
major health-care center in Nigeria, the country with the highest incidence of
sickle cell disease in the world with about 150,000 children born with the
disease annually, underscores the need for education of local health-care
providers as well as patient counseling and education. In addition, clinical
studies designed to assess the safety and efficacy of hydroxyurea in unique
African settings is needed to facilitate the introduction and utilization of
hydroxyurea in Nigeria and other parts of Africa.
-- Cognitive function impaired among sickle cell patients; transfusion trial
needed to assess how to mitigate brain damage, especially as patients age
[Abstract #428]
Elliott Vichinsky, MD, Children's Hospital and Research Center, Oakland, CA
Many consider brain dysfunction to be the most important and least-studied
problem afflicting the aging sickle cell population. About 25 percent of
neurologically intact sickle cell pediatric patients have neuropsychological
dysfunction -- a deficit in cognitive ability -- and silent central nervous
system (CNS) infarction -- death of tissue within the CNS system, including the
brain and spinal cord. In children, age is associated with a decline in
neuropsychological dysfunction, suggesting adults are at risk for progressive
brain injury.
This trial evaluated 138 adults with sickle cell anemia and 37 control
subjects with a series of cognitive tests that assessed verbal and nonverbal
intelligence, academic achievement, executive functioning, processing speed,
attention, and memory. Tests included the Wechsler Adult Intelligence Scale, the
Wechsler Memory Scale, the Woodcock-Johnson Tests of Achievement, the Test of
Everyday Attention, and others. MRI scans were also evaluated in 82 patients to
evaluate brain atrophy and lesions.
The study found that neuropsychological dysfunction and/or undetected brain
injury affect the majority of neurologically intact adults with sickle cell
anemia, especially in areas of executive functioning, reading, and math fluency.
In the study, 32 percent and 39 percent scored below 86 on the Wechsler Adult
Intelligence Scale Performance IQ and Processing Speed Index scores,
respectively, compared to 15 percent in national norms; 26 percent and 22
percent of patients scored below 86 on the Wechsler Memory Scale Visual
Immediate and Immediate Memory scales, respectively, compared to 15 percent in
national norms. Controlling for age, gender, and education, patients and
controls differed significantly on the Wechsler Adult Intelligence Scale
Processing Speed Index score and the Woodcock-Johnson score including reading,
math, and following directions. Sub-tests of the Test of Everyday Attention --
in attention and flexibility of thought -- showed significant decrease in
performance with age in sickle cell patients, but not in controls.
In 82 patients with MRIs, 63 percent had an abnormal MRI or
neuropsychological dysfunction, 38 percent had atrophy and/or ischemic lesions,
and 18 percent had ischemic lesions only. Low Performance IQ and Processing
Speed Index were significantly associated with ischemic lesions. Adjusting for
age and gender, hippocampal volume (the size of the hippocampus, the part of the
brain related to memory) in patients was 541.1 µL less than controls and
cerebrospinal fluid volume in patients was 16 mL greater than controls. These
differences are significant.
The level of hemoglobin (the oxygen-carrying molecule in the blood) was an
independent predictor of verbal IQ, Performance IQ, Processing Speed Index,
math, and executive function. Patients with lower hemoglobin scores had lower IQ
scores, and ischemic lesions alone did not account for the extent of the
neuropsychological impairment observed. Hemoglobin levels, age, and hippocampal
volume were predictive of the neuropsychological dysfunction, suggesting a link
between reduced oxygenation, neuronal loss, and cognitive impairment. These data
support the importance of future trials on transfusion and improvement of
neuropsychological function.
-- Sequential deferiprone-deferoxamine superior to deferiprone monotherapy,
the current "gold standard" in patients with thalassemia major
[Abstract #575]
Aurelio Maggio, MD, Hospital 'V. Cervello', Palermo, Italy
This five-year, multicenter, randomized trial evaluated two chelating
regimens in 140 patients with thalassemia major, a genetic disorder
characterized by the underproduction of hemoglobin, the molecule in red blood
cells that carries oxygen to all tissues. Chelating agents remove excess iron
from the body, a common problem in red blood cell disorders because of the
associated blood transfusions. Excess iron can lead to organ damage and heart
failure. This trial evaluated deferiprone monotherapy compared with sequential
treatment with deferiprone for four days followed by deferoxamine for three
days. While deferiprone is an oral drug, deferoxamine is administered via
subcutaneous infusion.
The study found that long-term use of sequential deferiprone-deferoxamine
treatment was more effective than the "gold standard" treatment of
deferiprone alone, with milder and reversible side effects, such as reversible
leukocytopenia (low number of white blood cells) and hypertransaminasemia, which
was defined as the increase of serum alanine transaminase levels up to two times
in comparison to normal values. In addition, after one year of treatment, the
deferiprone-deferoxamine group showed greater efficacy in terms of serum
ferritin level reduction than the deferoxiamine-only arm of a previous
randomized clinical trial in which a comparable cohort of patients were studied.
-- Deferasirox, an oral iron chelator, works as well as deferoxamine, which
requires subcutaneous injection, among sickle cell patients; possible
implications for improved patient compliance, reducing risk of organ damage
[Abstract #3395]
Elliott Vichinsky, MD, Children's Hospital and Research Center, Oakland, CA
This four-year extension trial among 185 patients with sickle cell disease is
a follow-up study to a one-year trial that showed that deferasirox and
deferoxamine were equally effective at reducing liver iron concentration. In
this four-year extension study, all patients stayed on deferasirox (n=132) or
were switched to the therapy (n=53). The trial showed that deferasirox
demonstrated dose-dependent efficacy in patients with sickle cell disease, with
a manageable tolerability profile and no new adverse events reported over a
median of 2.1 years of treatment. Because deferoxamine must be delivered via a
subcutaneous injection, patients must typically visit their doctor's office or
local clinic. Deferasirox is taken orally and therefore may support improved
patient compliance, a key factor in avoiding complications of iron overload,
including kidney damage.
In addition to sickle cell disease and thalassemia, press briefings will take
place at the annual meeting focusing on leukemias, hematologic malignancies,
blood clotting and bleeding disorders, and transplantation. The study authors
and press program moderator will be available for interviews after the press
program or by telephone. For the complete annual meeting sch