The California Institute for Regenerative Medicine has awarded MATTHEW PORTEUS, associate professor of pediatrics, a grant of $5.2 million to lay the groundwork for a clinical trial of a possible treatment for sickle cell disease.
Porteus has shown that he can take human blood stem cells with the gene defect that causes sickle cell disease and use gene-editing tools to repair the faulty gene. He also showed that he could successfully transplant those repaired blood stem cells into mice.
“We are extremely excited that, with CIRM support, we may be able to use gene correction to treat this terrible disease,” Porteus said.
Sickle cell disease damages tissues, causes pain and suffering and can even be life-threatening. It is caused by a single mutation in a gene that is the blueprint for one of the proteins in hemoglobin, the molecule that carries oxygen in red blood cells. Under certain conditions, red blood cells with the sickle cell defect will change from a soft, rounded form to a rigid, sickle shape. This change makes red blood cells clump together, clogging arteries and causing organ damage. There is currently no cure for the disease, and medical treatments are mostly restricted to efforts to limit the damage it can cause.
Porteus and his colleagues are preparing to conduct a clinical trial of the technique in patients with the disease. In such a trial, clinicians would draw participants’ blood, separate out their stem cells and then use a gene-editing tool called CRISPR to fix the sickle cell defect. After this, patients would be given a chemotherapy regimen that would kill off some of the patient’s defective stem cells, creating places in the bone marrow where the corrected blood stem cells could take up residence when they are given back to the patient. If the treatment worked, the repaired stem cells could possibly create enough normal red blood cells for the patient to be symptom-free for life.
The interdisciplinary team at Stanford includes researchers from the new Stem Cell and Gene Therapy Clinical Trials Office and the Laboratory of Cell and Gene Medicine. The grant from CIRM will be used to do the work necessary before asking the Food and Drug Administration to give the treatment the status of an investigational new drug, Porteus said. Getting this status is one of the last regulatory hurdles before a clinical trial can be put together.