By Drew Halley
A revolutionary new procedure for stem cell transplant is reversing the effects of severe adult sickle cell disease. For years, adults suffering from sickle cell anemia have relied on consistent blood transfusions and drug treatments to combat the disorder. Bone marrow transplants can reverse sickle cell, but have so far been restricted to children in the early stages of the disease. That is, until now.
Sickle cell anemia is a congenital blood disorder that affects all races, but is most common to persons with African ancestry, affecting about 72,000 in the US and millions worldwide. Red blood cells normally take the shape of a doughnut without its hole; in the blood of sickle cell patients, the cells assume an abnormal sickle shape. Sickle cells block small blood vessels and inhibit blood flow, which causes debilitating pain, damages organs and increases the risk of stroke. Many of the risks of sickle cell can be mediated through early diagnosis, dietary supplements, and drug treatment. But even with modern treatment, life expectancy for sickle cell patients is 42 in males, 48 in females. Some severe cases are resistant to existent therapies and can cut life even shorter.
Because red blood cells are produced in bone marrow, some high-risk children qualify for marrow transplants from a suitable sibling donor. Like all organ transplants, the procedure carries the danger of immune rejection, and so requires immunosuppressant drugs in addition to radiation therapy to kill diseased marrow. Transplants have been traditionally restricted to children, whose organs are comparably stronger than adults who suffer from the disease. Transplants are rare – there have been about 200 in the past few decades – and are attempted only in children whose disorders are life-threatening.
But a new procedure developed by the National Institute of Health (NIH) and Johns Hopkins University has successfully transplanted marrow to adults, reversing the disorder in 9 out of 10 patients. The new treatment uses significantly less radiation (about one fourth) to kill the patient’s existent marrow, combined with the immunosuppressant drug Sirolimus to reduce the likelihood of transplant rejection. By allowing more of the patient’s own marrow to remain, recovery from the transplant is faster and healthier (patients could previously spend months in germ-free isolation while their immune systems recovered). Thirty months after the transplant, the nine patients with successful transplants are healthy and show no side effects.
Many adults with sickle cell anemia take the drug hydroxyurea to treat the disorder. Hydroxyurea works by stimulating the body to produce a form of hemoglobin normally only found during development in the womb. The production of this hemoglobin type helps to balance the proportion of healthy vs. sickle cells in the blood, and reduces the damage done to lungs, kidneys, and liver (not to mention the risk of stroke). But hydroxyurea doesn’t work for all adult patients, making the prospect of adult marrow transplant a much-needed form of alternative therapy.
Kelly Halloway, the first half-match donation recipient at the National Institute of Health
So far, most adult patients who have received marrow transplants have had “full match” donors – siblings with a fully compatible genetic makeup. The chances of a sibling being fully matched are only 25%. But new procedures are expanding the pool of potential donors to “half match” donors, which includes parents and improves the likelihood of a compatible sibling to 75%. That means more sources of transplant marrow, and a better shot at a successful reversal of the disease.
Future research will aim to expand marrow transplants beyond sickle cell patients. Several other congenital blood diseases could conceivably be treated with marrow transplants, including such debilitating disorders as beta-thalassemia.Researchers are currently exploring the emerging possibilities of adult marrow transplants, and will doubtless yield more amazing treatments in coming years
Clear, honest information for people living with thalassemia — and the people who love them
Showing posts with label Bone. Show all posts
Showing posts with label Bone. Show all posts
Jun 14, 2010
May 22, 2009
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.
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.
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