Two gene therapies were approved by the FDA to edit the stem cells of patients 12 years and older with sickle cell disease. Sickle cell disease is caused by a gene mutation that makes red blood cells crescent-shaped instead of round, which can lower oxygen delivery and block blood vessels. The new treatments, though costly, effectively prevented the sickling, severe pain and organ damage that can occur with the disease.

Two gene therapies, Casgevy and Lyfgenia, were approved by the FDA to treat the most severe form of sickle cell disease (SCD) in eligible people over the age of 12. Casgevy uses the gene editing technology CRISPR. Lyfgenia uses a different technique that uses a virus to carry new genes to a cell. These therapies are not a cure, but are meant to drastically reduce symptoms.

SCD is a genetic blood disorder that affects 100,000 people in the US, and is most common in people of African descent. The gene is also present in people with Mediterranean, South American, Southeast Asian, and Middle Eastern ancestry.

SCD develops when a person inherits two copies of a gene (one from each parent) that causes a mutation in the hemoglobin protein of a red blood cell. The mutated hemoglobin protein causes the red blood cell to be sickle-shaped.

Sickled cells can stick together and block blood vessels which means tissues and organs don’t get enough oxygen. This is known as a “crisis” or vaso-occlusive events (VOEs) which is severely painful and can eventually damage organs.

The CRISPR technology in the Casgevy gene therapy works by turning off the gene that suppresses fetal hemoglobin. In other words, it allows the body to make the same form of hemoglobin that it used to make as a baby in utero. This fetal hemoglobin does not sickle, even when the gene that causes sickling is present.

The gene editing is done by removing a person's bone marrow cells, editing them, and returning the modified cells to the body. This process is long and involves a month's stay at the hospital in addition to high-dose chemotherapy.

The Lyfgenia technology also removes cells from a patient and puts them back in. Instead of using CRISPR technology, this technique uses a harmless virus to carry new DNA to the cell. The new gene codes for a new hemoglobin that is resistant to sickling. This method also involves a long hospital stay and high-dose chemotherapy.

In clinical trials for CRISPR, 96% of patients had no pain crisis events for the 18 months of the study. This number was 88% for the Lyfgenia treatment. While these therapies are not cures for the disease, they are meant to be one-time treatments that help keep red blood cells round and healthy and prevent pain crises.

The only known cure for SCD is a bone marrow transplant, but it is often hard for patients to find a good donor match and not everyone is eligible due to the risks involved.

The cost of the Casgevy CRISPR therapy and Lyfgenia gene therapy is high, leading to concerns about who will be able to access these therapies, and where payment will come from. Other medical costs include a required month's stay at the hospital or the cost of chemotherapy. Long-term monitoring is needed to see how long the effects last and to monitor patients for potential complications or side effects of the treatment. The Lyfgenia treatment comes with a safety warning from the FDA.