The California Institute for Regenerative Medicine (CIRM) awarded Matthew Porteus, a Stanford University associate professor of pediatrics, a $5.2 million grant to conduct the groundwork leading to a clinical trial of a possible treatment for sickle cell disease (SCD).
SCD develops when a gene is mutated that codes for a subunit of hemoglobin, the protein that carries oxygen in red blood cells. Certain red blood cells with the sickle cell defect can change from a soft, rounded form into a rigid, sickle shape, making red blood cells clump together. These clumps can lead to clogged arteries and cause organ damage and extreme pain.
The grant follows Porteus’ research, which has shown that human blood cells with the mutation that causes sickle cell disease can be taken and re-built with gene-editing tools to repair the faulty gene. In animal studies, Porteus showed that he could also successfully transplant the repaired blood stem cells back 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 in a press release.
Porteus and his team will prepare a study to evaluate this technique in human patients with SCD. When the trial starts, clinicians will draw blood from participants, separate out their stem cells, and then use a gene-editing tool called CRISPR to fix the sickle cell defect.
At that point, clinicians will begin giving participants a chemotherapy regimen aimed at killing off some of their defective stem cells, creating space in the bone marrow for the repaired blood stem cells to settle after they’ve been transplanted back into the patients.
If the treatment works, the repaired stem cells will hopefully create enough normal red blood cells to allow sickle cell disease patients to live their lives free of symptoms.
The money from the CIRM grant will be used to do all work needed before submitting an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA). The FDA’s approval of an IND status for the therapy candidate is one of the final regulatory requirements needed before a clinical trial can be launched.
The Stanford interdisciplinary team that will assist Porteus includes researchers from the new Stem Cell and Gene Therapy Clinical Trials Office and the Laboratory of Cell and Gene Medicine.
Gene therapy is a trending experimental method that uses gene editing to treat or prevent disease. When perfected, this technique could allow the treatment of a disorder by inserting a gene into patients’ cells rather than using drugs or surgery. There are several approaches to gene therapy to fight diease, including replacing mutated genes with healthy copies, inactivating a mutated gene, or introducing a new gene in the body.
Because gene therapy is not yet risk-free, it is first being tested in diseases that have no known cures, such as SCD. The treatments available today for sickle cell patients are primarily directed at limiting the damage caused by SCD.