Promising evidence for sickle cell gene therapy found in new study

New research published in the New England Journal of Medicine indicates that stem cell gene therapy may offer a promising, curative treatment for the painful, inherited blood disorder sickle cell disease (SCD). The findings from a new clinical trial add to the body of evidence supporting gene therapy as a treatment for sickle cell disease, which primarily impacts people of color. Until recently, the only treatment options have been intensive bone marrow transplants from siblings or matched donors.

As part of the trial, researchers used CRISPR-Cas9 to edit specific genes in stem cells — the building blocks of blood cells — taken from each patient. The edits increased the cells’ production of fetal hemoglobin (HbF), a protein that can replace unhealthy, sickled hemoglobin in the blood and protect against the complications of sickle cell disease. The patients then received their own edited cells as therapeutic infusions.

The therapy was the second for this disease to use CRISPR-Cas9 technology and the first to target a new genetic area and use cryopreserved stem cells with the hope of increasing access to such a treatment. Other gene therapy studies for SCD have used lentiviruses — a type of virus often modified and used for gene editing which remain in the cell long-term. No foreign material remains in stem cells edited with CRISPR-Cas9.

Trial participants who received the CRISPR-edited stem cells reported a decrease in vaso-occlusive events, a painful phenomenon that occurs when sickled red blood cells accumulate and cause a blockage.

Reference: CRISPR-Cas9 Editing of the HBG1 and HGB2 Promoters to Treat Sickle Cell Disease, New England Journal of Medicine, DOI 10.1056/NEJMoa2215643