Antidepressant could reverse sickle cell disease
Blood smears from normal (left) and sickle cell disease (right). The arrows show the rigid, sickle-shaped cells.--Courtesy of University of Michigan Health System
A 'mood enhancer' drug used to manage depression since the 1960s may also be effective at treating patients with sickle cell anemia, a painful genetic disorder.
Researchers at the University of Michigan Medical School tested tranylcypromine, or TCP, in mice to find that the drug essentially reverses the effects of sickle cell disease, a condition in which a person's misshapen red blood cells cause vascular damage and premature death.
The discovery is a culmination of years' worth of research. The researchers first pinpointed LSD1, a molecule inside red blood cells, as a drug target. That's because LSD1 plays a key role in blocking the production of the fetal form of hemoglobin. Then after a search for drugs that act on LSD1, scientists tested TCP in mice. The scientists noted that it blocked LSD1 and boosted the production of fetal hemoglobin--counteracting the devastating effect of the abnormal hemoglobin S that sickle cell patients make. The study findings were published in Nature Medicine.
"This is the first time that fetal hemoglobin synthesis was re-activated both in human blood cells and in mice to such a high level using a drug, and it demonstrates that once you understand the basic biological mechanism underlying a disease, you can develop drugs to treat it," Doug Engel, senior author of the study and chair of U-M's Department of Cell & Developmental Biology, said in a statement.
While the scientists say it is too soon for the drug to be used in routine treatment of the disease, they are planning a clinical trial for adult patients who have the life-threatening condition. The discovery could also lead to other therapies for the disease.
Sickle cell is most commonly treated with oral hydroxyurea, which works by increasing fetal hemoglobin production. Transfusions and bone marrow transplants from unrelated donors are other treatment methods, which aim to exchange the source of the overall red blood cell supply.