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Scientists identify potential drug target for treatment-resistant anemias
Date:6/9/2013

CAMBRIDGE, Mass. (June 9, 2013) Researchers at Whitehead Institute have identified a protein that is the target of glucocorticoids, the drugs that are used to increase red blood cell production in patients with certain types of anemia, including those resulting from trauma, sepsis, malaria, kidney dialysis, and chemotherapy. The discovery could spur development of drugs capable of increasing this protein's production without causing the severe side effects associated with glucocorticoids.

"This research is medically important, and we are using it to find a better way to increase the production of red blood cells for these patients," says Harvey Lodish, who is a Whitehead Institute Founding Member and a professor of biology at MIT. "It is also a new insight into how self-renewal in stem cells can be controlled, and a new way to think about how we can use an RNA binding protein to maintain stem and progenitor cells."

Anemia occurs due to a breakdown in erythropoiesis, the multi-step process that creates red blood cells. Some common anemias can be treated with a recombinant form of the hormone erythropoietin (EPO), which normally stimulates red blood-cell production at a fairly late stage of erythropoiesis.

However, certain anemias fail to respond to EPO, creating a large unmet medical need. In the case of Diamond Blackfan anemia (DBA), patients lack a sufficient number of EPO-responsive cells. Instead, glucocorticoids such as prednisone or prednisolone are used to treat DBA and other anemias resistant to EPO by increasing the numbers of the later progenitor cells that respond to EPO. These drugs cause a host of negative side effects, including decreased bone density, immunosuppression, stunted growth, and cataracts, all of which are particularly burdensome for young patients.

Earlier work in the Lodish lab determined that glucocorticoids increase red blood cell production by acting on early progenitors of red blood cells, call
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Contact: Nicole Rura
rura@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

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