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Could an old antidepressant treat sickle cell disease?
Date:2/19/2013

ANN ARBOR, Mich. An antidepressant drug used since the 1960s may also hold promise for treating sickle cell disease, according to a surprising new finding made in mice and human red blood cells by a team from the University of Michigan Medical School.

The discovery that tranylcypromine, or TCP, can essentially reverse the effects of sickle cell disease was made by U-M scientists who have spent more than three decades studying the basic biology of the condition, with funding from the National Institutes of Health.

Their findings, published in Nature Medicine, pave the way for a clinical trial now being planned for adult patients who have the life-threatening condition. The discovery may also lead to other treatments for the disease, which leads misshapen red blood cells to cause vascular damage and premature death.

But the researchers caution it is too soon for the drug to be used in routine treatment of sickle cell anemia, an inherited genetic disease that affects tens of thousands of Americans and millions of others worldwide.

The climax of a decade of discovery

In the new paper, the researchers describe a painstaking effort to test TCP's effect on the body's production of a particular form of hemoglobin the key protein that allows red blood cells to carry oxygen.

The drug acts on a molecule inside red blood cells called LSD1, which is involved in blocking the production of the fetal form of hemoglobin. The U-M team zeroed in on the importance of LSD1 as a drug target after many years of research.

Then, they literally did a Google search to find drugs that act on LSD1. That's how they found TCP, which since 1960 has been used to treat severe depression.

In the new paper, they describe how TCP blocked LSD1 and boosted the production of fetal hemoglobin -- offsetting the devastating impact of the abnormal "adult" form of hemoglobin that sickle cell patients make.

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Contact: Kara Gavin
kegavin@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert  

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