The UK has today become the first country to give regulatory approval to a medical procedure that uses CRISPR gene editing. The Medicines and Healthcare products Regulatory Agency (MHRA) has approved Casgevy, a therapy to be used to treat sickle cell disease and beta thalassemia (also called β -thalassemia).
[Related: CRISPR breaks ground as a one-shot treatment for a rare disease.]
What are sickle cell anemia and beta thalassemia?
Both diseases are painful, lifelong genetic conditions caused by errors in the genes for a protein called hemoglobin. Red blood cells use hemoglobin to carry oxygen around the body. Sickle cell disease is particularly common among people of Caribbean or African descent. Abnormal hemoglobin makes blood cells crescent-shaped and hard. The deformed cells then stick together and block the flow of oxygen to the organs, causing severe pain. The cells can then die early, leading to anemia.
Beta thalassemia predominantly affects patients of Mediterranean, South Asian, Southeast Asian and Middle Eastern descent. It also causes anemia because the fashion can’t make as much hemoglobin.
Casgevy was developed by Vertex Pharmaceuticals of Boston and Crispr Therapeutics of Switzerland and can be used to replace bone marrow transplants. The companies estimate that approximately 2,000 people in the UK are already eligible for the therapy.
“I am pleased to announce that we have authorized an innovative and first-of-its-kind gene-editing treatment called Casgevy, which has been shown in trials to restore healthy hemoglobin production in most participants with sickle cell anemia and transfusion-dependent beta thalassemia , alleviating the symptoms of the disease,” MHRA interim executive director of quality and access to healthcare Julian Beach said in a statement.
How does Casgey use CRISPR gene editing?
The new treatment uses the CRISPR-Cas9 gene-editing technique, which allows scientists to make precise changes to human DNA. French microbiologist, geneticist and biochemist Emmanuel Charpentier and American biochemist Jennifer A. Doudna, who shared the 2020 Nobel Prize in Chemistry for their work.
Casgevy uses stem cells taken from a patient’s bone marrow. The cells are then transferred to a lab and the genes that are meant to include a functioning version of hemoglobin are edited with CRISPR. According to the MHRA, patients should undergo ‘conditioning treatment’. This may involve taking a drug that suppresses the immune system, radiation therapy or chemotherapy to prepare the body for infusing CRISPR-modified cells back into the body. The new treatment does not come with the risk of a graft-versus-host reaction, as with a traditional bone marrow transplant.
[Related: These organisms have a natural gene-editing system that could be more useful than CRISPR.]
After the infusion, patients may need to stay in a hospital for at least a month. During this time, the treated cells will begin to “settle” in the bone marrow and produce red blood cells that have a stable form of hemoglobin.
While seeking regulatory approval, the researchers conducted a clinical trial of 45 patients with sickle cell disease. Of that group, 29 patients were in the trial long enough for researchers to measure how effective Casgevy was. Of these eligible patients, 28 were free of severe pain crises at least 12 months after treatment.
In the clinical trial of 54 patients with transfusion-dependent beta thalassemia, 42 patients participated in the trial long enough to determine efficacy. Of these, 39 did not need a red blood cell transfusion at least 12 months after treatment. The other three had more than a 70 percent reduction in the need for red blood cell transfusions.
“This is a great step in advancing medical approaches to tackle genetic diseases that we never thought possible to cure,” University of Hertfordshire geneticist Alaina Pance said in a statement released by the Science Media Center. “Modifying stem cells from the patient’s bone marrow avoids the problems associated with immune compatibility, i.e. the search for donors who match the patient and the subsequent immunosuppression, and constitutes a true cure of the disease, not a cure.’
The US Food and Drug Administration is evaluating the same treatment. On Oct. 31, an FDA advisory committee said the treatment is safe for patients. The decision is expected to be made by December 8.
The cost of the therapy has not been announced, but it is likely to be expensive.
Despite its potential for good, CRISPR is tainted by controversy and ripe for debate over fears of being able to select genes for so-called “designer babies.” In 2018, Chinese scientist He Jiankui announced that he had created the world’s first gene-edited babies. He was found guilty of “illegal medical practice” and sentenced to 3 years in prison. This work has fueled the debate over how best to regulate this powerful technique, with many saying it should not be used to edit human genes that will be passed on to the next generation.
Other experiments and trials using the gene editing technique in rare diseases are ongoing. In 2021, a clinical trial began for a drug called NTLA-2001, researchers tried to treat six people with a rare genetic disease called transthyretin amyloidosis with technology that delivers CRISPR directly to cells in the liver. The FDA cleared the trial to enter its critical third phase in October.