Scientists Discover Genetic Target to Treat Sickle Cell Disease

Sickle cell disease (SCD) can be a huge problem for humans. In fact, it affects almost 100,000 just in the United States and millions worldwide. Now, though, researchers have discovered a new genetic target for potential therapy for SCD. The findings could lead to new treatments that could help people cope with this disease.

The new target itself is called an enhancer. It controls a molecular switch it red blood cells called BCL11A that then regulates hemoglobin production. Previous work has shown that BCL11A causes red blood cells to produce fetal hemoglobin that, in SCD patients, is unaffected by the sickle cell mutation and counteracts the deleterious effects of sickle hemoglobin. This makes BCL11A an attractive target for treating SCD.

There are problems, though. BCL11A also plays important roles in other cell types, including the immune system's antibody-producing B cells. This raises concerns that targeting BCL11A could have unwanted consequences for patients.

In order to better understand how to specifically target cells, the scientists discovered that some patients with SCD spontaneously produce higher levels of fetal hemoglobin and enjoy an improved prognosis. These individuals possessed naturally occurring mutations that function to weaken the enhancer, turning BCL11A's activity down and allowing red blood cells to manufacture some fetal hemoglobin.

"This is a very exciting study," said Feng Zhang, a specialist in genome engineering who was not involved in the study, in a news release. "The findings suggest a potential new approach to treating sickle cell disease and related diseases, one that relies on nucleases to remove this regulatory region, rather than an exogenous gene as in class gene therapy."

The findings are important for future treatments for SCD. In addition, it could allow those coping with the condition to eventually have a complete cure. Moving forward, the scientists hope to develop treatments to do just that.

The findings are published in the journal Science.