Breakthrough in sickle cell disease and thalassemia research

Researchers have identified a gene that directly affects the production of a form of hemoglobin that is instrumental in modifying the severity of the inherited blood disorders sickle cell disease and thalassemia.

The discovery could lead to breakthrough therapies for sickle cell disease and thalassemia, which could potentially eliminate the devastating and life-threatening complications of these diseases, such as severe pain, damage to the eyes and other organs, infections, and stroke.

"Human Fetal Hemoglobin Expression is Regulated by the Developmental Stage-Specific Repressor BCL11A," is published online in Science December 4. The study was conducted by researchers at Children's Hospital Boston and Dana-Farber Cancer Institute and supported by the National Institutes of Health's National Heart, Lung, and Blood Institute (NHLBI) and National Institutes of Diabetes and Digestive and Kidney Diseases, and by the Howard Hughes Medical Institute.

Hemoglobin is the protein in red blood cells that carries oxygen to the body's tissues. In sickle cell disease, hemoglobin is abnormal and sticks together. The red blood cells become stiff and sickle-shaped, causing them to block blood vessels and rob tissues of necessary blood and oxygen. In thalassemia, the body has trouble producing adult forms of hemoglobin.

Other studies have shown that in patients with sickle cell disease, those who continue to produce fetal hemoglobin (HbF) have much milder forms of sickle cell anemia. For years, scientists have sought ways to increase HbF production in patients with sickle cell disease and thalassemia.

Researchers report that by suppressing a gene called BCL11A, HbF production improves dramatically. Their findings provide new insights into the mechanisms involved in the body's switch from producing fetal hemoglobin to adult hemoglobin and identify a potential new target for therapies that could dramatically alter the course of sickle cell anemia and thalassemia.

The researchers built upon their recently reported results of genome-wide association studies that identified several gene variants associated with HbF levels. BCL11A was found to have the greatest effect on HbF levels. In the follow-up study reported today, they report that BCL11A encodes a transcription factor that directly suppresses HbF production.

A drug therapy that increases HbF levels enough to modify the severity of sickle cell disease is currently available. The drug hydroxyurea was approved by the FDA in 1998 to prevent pain crises in adults with sickle cell disease after studies showed that it increases fetal hemoglobin production, reduces the damaging effects of sickle cell disease, and improves some aspects of quality of life. Use of hydroxyurea is limited, however, in part because not all patients respond to the drug, and there are short-term and long-term adverse effects. New therapies targeting BCL11A would be the first to directly affect the natural processes involved in increasing HbF.

WHO: Alan Michelson, M.D., Ph.D., NHLBI associate director for basic research, and Susan Shurin, M.D., NHLBI deputy director and acting director of the NHLBI Division of Blood Diseases and Resources, are available to comment on these findings.

WHY: Sickle cell disease is the most common inherited blood disorder. In the United States, it affects approximately 70,000 people, primarily African Americans. Worldwide, sickle cell anemia affects millions of people and is found in people whose families come from Africa, South or Central America (especially Panama), Caribbean islands, Mediterranean countries, India, and Saudi Arabia.

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. In addition, people with sickle cell disease have a shortened life expectancy due to infections, lung problems, and stroke.

Treatments developed over the past three decades have led to the doubling of the life expectancy of sickle cell disease patients between 1972 and 2002. These treatments include medications, blood and bone marrow transfusions, and other procedures to relieve or prevent complications. Until now, however, scientists could not directly target processes known to affect the severity of sickle cell disease.

Ninth Cooley's Anemia Symposium

Sponsored by the Cooley's Anemia Foundation and the New York Academy of Sciences

Thanks to scientific advances, individuals with thalassemia, a group of genetic blood disorders which includes Cooley's Anemia, are now living into their 40's and 50's. Not only are individuals living longer, but their quality of life has increased. Scientific and clinical advancements have resulted in new iron-chelating drugs, early detection of organ failure, an understanding of adult complications associated with living with thalassemia (osteoporosis, heart failure, growth hormone defi ciency, pulmonary hypertension, and in fertility) and promising progress towards the ultimate magic bullet, a cure in the form of bone marrow and cord blood transplants, or gene therapy.

The symposium will integrate basic science and clinical research so that both scientists and clinicians can develop a mutual understanding of recent progress in thalassemia. Patients are also welcome to attend the symposium and are eligible for discounted prices. Please email info@cooleysanemia.org or call 800. 522.7222 for more information.

For conference brochure including full agenda, please click here.

Scientific Organizing Committee:

Elliott Vichinsky, MD
Director, Hematology/Oncology
Children's Hospital and Research Center in Oakland, CA
Ellis Neufeld, MD, PhD
Associate Chief, Division of Hematology/Oncology
Children's Hospital Boston

Plenary Sessions on:

Iron Regulation and Metabolism
Gene Regulation and Therapy
Iron Overload and Chelation Therapy
Iron Imaging
New Advances in Stem Cell
Transplantation
New Therapy For Hemoglobin F
Cardiac Dysfunction
Nutrition and Antioxidant Therapies
Clinical Syndromes in Thalassemia and Disease Severity
The Adult Thalassemia Patient

CALL FOR ABSTRACTS
Deadline for abstract submission is Friday, August 14, 2009. For complete abstract instructions, please e-mail: cooleys@nyas.org. Type the words "Abstract Information" in the subject line - no need to type a message. Instructions will be forwarded automatically. Any questions, please call 212.298.8681.

Travel Fellowships may become available. Please return to this website for future updates.

For sponsorship opportunities please contact Sonya Dougal at sdougal@nyas.org or 212.298.8682.

The project described was supported by Award Number R13HL096359 from the National Heart, Lung, And Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, And Blood Institute or the National Institutes of Health.

The Thalassemia Action Group (TAG), the only national patient support group for thalassemia patients, will host a one-day meeting in conjunction with this conference. The meeting, to be held on Saturday October 24th from 9:00 am to 5:00 pm, is intended for patients and family members in order to educate them on presentations and scientific advancements discussed during the symposium. It is a chance for patients to hear experts on thalassemia, ask questions and discuss the concerns that face those afflicted with thalassemia. For more information please visit www.cooleysanemia.org or email info@cooleysanemia.org. For information about registration to the TAG meeting please call 800.522.7222 (ext 205).
Dissemination Material
Listen to the eBriefing from the last Cooley's symposium at www.nyas.org/Cooleys
Read publications from our previous Cooley's Symposia at www.nyas.org/CooleysAnnals

NIH Announces Funding Opportunity

The National Institutes of Health announced a new funding opportunity of interest to the thalassemia community on May 1, 2009. Below is information from that announcement.



Purpose. This Funding Opportunity Announcement (FOA) is a call for the application of imaging and other non- or minimally-invasive technologies to detect, characterize, diagnose, identify persons with predisposition to, or monitor treatment of diseases of interest to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH). Also needed are new, robust surrogate markers for clinical trial endpoints, and new ways to characterize normal and pathological tissues in vivo. Diseases of interest include type 1 and 2 diabetes; acute and chronic kidney disease, liver, urologic, hematologic, digestive, endocrine, and metabolic diseases and their complications; obesity; obesity-related hypertension, hypertension, renal and vascular disorders leading to hypertension. Applicable techniques include molecular imaging and functional imaging approaches, imaging methods with high spatial, chemical or time resolution, metabolomics, proteomics, genomics, or new spectroscopic or sensor array technologies for monitoring metabolic or physiological events. Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) award mechanism. Developmental/Exploratory Research (R21) applications within the scientific scope of the FOA can be submitted in response to the NIH Parent R21 PA, http://grants.nih.gov/grants/guide/pa-files/PA-09-164.html.
Non-Invasive Methods for Diagnosis and Progression of Diabetes, Kidney, Urological, Hematological and Digestive Diseases and Hypertensive Disorders (R01)