Gene may open door for new sickle cell therapies

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CHICAGO (Reuters) – U.S. researchers have discovered a gene switch that could lead to better treatments for sickle cell disease and thalassemia, two inherited blood disorders that affect millions of people, they said on Thursday.

Learning how to activate this switch might help doctors direct the body to make healthier blood cells — in this case, replicating conditions found in the womb.

People with these blood disorders either make too little or abnormal forms of hemoglobin, the protein in red blood cells that is vital for carrying oxygen to the body’s tissues.

A developing fetus uses one gene to make hemoglobin, but switches to another after birth, and problems with this adult gene are what lead to sickle cell disease and thalassemia.

“One of the goals for many years has been to understand this switch of hemoglobins, with the idea that if you could understand it you could reverse it or reactivate (the fetal gene),” said Dr. Stuart Orkin of Harvard Medical School in Boston, who reported his findings in the journal Science.

Orkin and colleagues said a gene called BCL11A directly affects the production of fetal hemoglobin.

“This one is a major player,” Orkin said in a telephone interview, calling BCL11A a “silencer gene” responsible for keeping fetal hemoglobin in check. “It is probably not the only player but we think it is a significant player,” he said.

Orkin said some people continue to make fetal hemoglobin after they are born, and those who do and have sickle cell disease have much milder symptoms.

In experiments on normal human cells, Orkin said his team was able to turn off the activity of this gene, and the cells produced more fetal hemoglobin.

Orkin said the finding offers hope for new therapies, including gene therapy or new drugs that could modify the effects of the BCL11A gene.


“This is a little bit of a holy grail,” said Dr. Susan Shurin, deputy director of the National Heart, Lung and Blood Institute, which helped fund the research.

“Over the past 40 years people have looked really hard to understand what kinds of things control the switch from fetal to adult hemoglobin,” she said in a telephone interview.

“What this does is it opens up the potential for some highly targeted therapeutic intervention.”.

Shurin said an older drug called hydroxyurea, approved by the U.S. Food and Drug Administration in 1998, increases production of BCL11A, but not all patients benefit and it has some toxic side effects.

She said the research by Orkin and others really paves the way for new drug development. “It gives you methods you can use to screen agents that are likely to be effective,” she said.

In sickle cell disease, blood cells become stiff and sickle-shaped, causing them to block blood vessels and starve tissues of oxygen. In thalassemia, the body struggles to make enough hemoglobin, resulting in anemia that can leave the body prone to infection.

Sickle cell disease is the most common inherited blood disorder, affecting about 70,000 people in the United States, mostly African Americans. It affects millions of people worldwide.

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