Until recently, the only possible cure for sickle cell disease, an inherited genetic blood disorder common in people with African ancestry, was a bone marrow transplant, which has its own set of challenges.
Today, people with sickle cell disease (SCD) that affects an estimated 100,000 Americans and can cause chronic pain, organ damage, stroke, and shortened life expectancy have an additional, potentially curative options. In early December, the Food and Drug Administration (FDA) approved two gene therapies for SCD, one of which is the first approved drug that uses the gene-editing tool CRISPR.
Both treatments Casgevy, made by Vertex Pharmaceuticals and CRISPR Therapeutics, and Lyfgenia, by Bluebird Bioare are for people 12 years and older. Sickle cell disease is a red blood cell disorder that affects hemoglobin, the protein that carries oxygen throughout the body. These two therapies work in different ways, but both are meant to be a one-time fix, although that will take years of follow-up to know for sure.
With Casgevy, an edit (or cut) is made to a particular gene to reactivate the production of fetal hemoglobin, which dissolves the faulty red blood cells caused by sickle cell disease. cell (more below). Lyfgenia, on the other hand, uses a viral envelope to deliver a healthy gene that produces hemoglobin.
The therapies have been hailed as groundbreaking because they represent the first gene therapies to potentially cure a hereditary condition.
For many years, we had only one treatment for sickle cell disease, and then medicine advanced to the point where we could offer bone marrow transplants, the first potential cure for sickle cell disease, says Cece Calhoun, MD, MBA, a hematologist at Yale Medicine. – oncologist. But trying to find a good match for a transplant is a big hurdle. This new technology uses gene therapy to allow patients to become their own match.
This is important, he said, because the sickle cell crisis the pain caused by the disease is unpredictable and severe, similar to what it feels like to have a long bone fracture.
However, according to Dr. Calhoun, the disease caused by sickle cell disease is not the only problem that people with the condition face.
Sickle cell disease affects every organ. Children are having strokes, and young adults in their 30s are experiencing kidney failure from sickle cell disease. If we can intervene and prevent these complications and allow these patients to live full lives, that’s great, said Dr. Calhoun.
Lakshmanan Krishnamurti, MD, chief of Yale Medicine Pediatric Hematology & Oncology, agrees.
Many cannot do a bone marrow transplant because only about 15% of patients have a matching sibling, and we can find an unrelated donor in another 10% to 12%. That means we only help 25% of patients, says Dr. Krishnamurti, who is an author of the Lyfgenia study published in The New England Journal of Medicine. This is a big step forward.
However, gene therapies take a year to complete and the process is tedious. Like bone marrow transplants, they require high-dose chemotherapy to kill the faulty stem cells before they can be replaced with modified stem cells.
Gene therapies are only available in large, authorized medical centers because they require advanced care. They are also expensive (estimated at $2 to $3 million per patient), and it has not been determined whether or how insurance companies, including Medicaid, will cover the treatment.
Dr. Krishnamurti says both treatments are available at Yale and that anyone interested in learning more should talk to their doctor.
Below, Dr. Calhoun and Krishnamurti answer common questions about sickle cell disease and these new gene therapies.
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