Patients with sickle cell disease have a mutation in the beta-haemoglobin gene, causing them to produce misshapen red blood cells that can block blood vessels leading to severe pain, anaemia and potentially life-threatening complications, such as organ damage and strokes. Currently, the only cure is a stem cell transplant from a healthy donor, but in the newly-approved trial, scientists from the University of California will use CRISPR/Cas9 genome editing to replace the faulty gene with a functional version.
'Gene therapy and genome editing allow each patient to serve as their own stem cell donor,' said Professor Donald Kohn, from the Broad Stem Cell Research Centre at the University of California Los Angeles, one of the clinical trial leaders. 'In theory, these approaches should be much safer than a transplant from another person and could become universally available because they eliminate the need to find the needle in a haystack that is a matched stem cell donor.'
In the trial, blood stem cells will be harvested from the patients and grown in the lab. CRISPR/Cas9 will be used to 'cut and replace' a sequence of DNA containing the mutation with a healthy copy. The edited cells will then be returned to the patient's body in the same way they would be if the patient was receiving donor stem cells.
'The goal of this form of genome editing therapy is to correct the mutation in enough stem cells so the resulting blood in circulation has corrected red blood cells,' said Dr Mark Walters, from the University of California San Francisco Benioff Children's Hospital, another of the clinical trial leaders.
The study will take place over four years, and include six adults and three adolescents with severe sickle cell disease, testing both safety and efficacy.
The treatment does have risks: the patients will need to have high dose chemotherapy, to kill all remaining blood stem cells before the modified stem cells are put back. This is also necessary before receiving donor stem cells and can cause severe side effects as the patient's immune system is temporarily disabled.
A similar trial, using CRISPR/Cas9 to activate bone marrow stem cells to produce an alternative version of haemoglobin, rather than correcting the faulty version, has recently shown promising results in a patient with sickle cell disease (see BioNews 1052).