Gene therapy flips switch in sickle cell disease

Therapy pushes cells to produce fetal form of oxygen-binding protein
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A gene therapy that flips a switch and turns on healthy hemoglobin production could be a step toward treating sickle cell disease, a painful inherited disorder caused by a single mutation in the hemoglobin gene.

Rather than replacing the mutated gene, the Dana-Farber/Children's Hospital Cancer Center (DF/CHCC) researchers are taking a different approach. Before and for about 6 months after birth, babies produce fetal hemoglobin, which is then switched over to the adult form by the molecular switch known as BCL11A. The researchers are targeting the switch using gene therapy, switching cells back to producing the fetal form, which is better at binding oxygen and at least partly compensates for the damaging effects of the mutated adult form.

In results presented at the 54th annual meeting of the American Society of Hematology (ASH), the researchers were able to turn down production of the molecular switch and increase the production of fetal hemoglobin in mice five- to twentyfold with no toxicity. As the researchers noted, though, this is early-stage research and they haven't tried it yet in an animal model of sickle cell disease.

"There are many approaches to sickle cell disease, and while we've shown we can develop viral vectors, knock down BCL11A, and induce fetal hemoglobin production, it's all been done in non-disease model systems," cautioned Raffaele Renella of DF/CHCC. "What we don't yet know is whether we can stop production of sickled cells in a sickle cell system. Further experiments will show us if that is possible."

- read the press release
- see the abstract

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