Turning back the Clock in Inherit...( Reawakening ...),Health

Reawakening a dormant gene could ease sickle-cell disease and thalassemia

(Vocus) December 4, 2008 -- Researchers at Children's Hospital Boston (www.childrenshospital.org) and Dana-Farber Cancer Institute have identified a way to get red blood cells to produce a form of hemoglobin normally made only before birth or by young infants. This could potentially transform sickle-cell disease and beta-thalassemia -- life-threatening inherited anemias -- into benign or nearly benign conditions. The findings were published by the journal Science, in its online Science Express, on December 4.

After birth, babies gradually switch from producing fetal hemoglobin (HbF) to an adult form. From population studies, it's been known for many years that people who retain the ability to produce HbF have much milder forms of anemia. Attempts to develop therapies to reactivate HbF directly have been hampered by a lack of understanding of how HbF production is switched off. The drug hydroxyurea often raises HbF in patients, but responses are not uniform and there are potential side effects.

Seeking a better approach, researchers Stuart Orkin, MD, a Howard Hughes Medical Institute investigator at Children's Hospital Boston, and Vijay Sankaran, an MD-PhD student in Orkin's lab, in collaboration with researchers at the Broad Institute of Harvard and MIT, capitalized on comprehensive gene association studies that identified DNA sequence variants (altered strings of genetic code) that correlate with HbF levels. In a study published last July, they identified five variants that influence HbF levels and disease severity in a group of 1600 patients with sickle-cell disease, the most common inherited blood disorder in the United States.

The variant with the largest effect on HbF levels contains a g
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