Sickle cell disease therapy hits major milestone on path to clinical trial

Nancy Rene’s grandson has sickle cell disease. Read her Story of Hope on our website.

Combining stem cell therapy with gene therapy looks like it can dramatically improve the safety of a therapy that has cured sickle cell disease in a few patients. Currently physicians reserve that therapy for those children with the most severe symptoms because the therapy itself carries significant risk.

The inherited mutation that causes sickle cell disease results in blood-forming stem cells that produce red blood cells with a deformed version of hemoglobin, the part of the blood that carries oxygen around the body. That defective protein causes red blood cells to be rigid and get stuck in small blood vessels causing severe pain and sometimes strokes.

The current therapy gives children new blood forming stem cells that have the correct version of the hemoglobin gene, but those stem cells come from bone marrow from a donor. That type of transplant carries significant risk of rejection and other potentially life-threatening side effects.

So a CIRM-funded Disease Team at the University of California, Los Angeles led by Donald Kohn has developed a procedure in which they harvest blood-forming stem cells directly from the patient. Then, in the lab, they use a virus to carry the correct hemoglobin gene into the cells. The team showed that these altered stem cells can produce red blood cells with the correct hemoglobin in the lab. They also showed that it worked when they transplanted the cells into a mouse.

The Journal of Clinical Investigation published the results online yesterday and UCLA issued a press release quoting Kohn on the results:

“The results demonstrate that our technique of lentiviral transduction is capable of efficient transfer and consistent expression of an effective anti-sickling beta-globin gene in human SCD bone marrow progenitor cells, which improved the physiologic parameters of the resulting red blood cells.”

You can read more about the CIRM Disease Team project here, along with information about other sickle cell projects we’ve funded.

It was fun to see this milestone toward a new use for blood-forming stem cells come out on the 25th anniversary of the first ever isolation of those cells by CIRM grantee Irving Weissman, which we wrote about yesterday.

CIRM funding: Donald Kohn (DR1-01452)

Don Gibbons

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