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First CRISPR Therapy Approved for a Genetic Disease in the United Kingdom

A decade ago, CRISPR promised to revolutionize medicine. Now, Casgevy, a pioneering therapy developed by Vertex Pharmaceuticals and CRISPR Therapeutics, has received approval in the United Kingdom for sickle cell anemia and beta-thalassemia.


Just over a decade ago, the scientific community glimpsed the revolutionary potential of CRISPR technology to transform the treatment of genetic diseases. Today, we celebrate an extraordinary milestone: the approval of Casgevy, the first CRISPR therapy for sickle cell anemia and beta-thalassemia, granted by the UK's drug regulatory agency. Developed by Vertex Pharmaceuticals in collaboration with CRISPR Therapeutics, this therapy opens new possibilities for patients who have faced the challenge of debilitating genetic diseases for far too long.

 

Sickle cell anemia and beta-thalassemia as therapeutic targets


The cells have a sickle shape, they are not flexible, and they adhere to the walls of blood vessels causing a blockage.

Both diseases are blood disorders caused by mutations in the HBB gene, affecting the production of hemoglobin.


En the case of sickle cell anemia, a mutation causes red blood cells to take an abnormal shape under low-oxygen conditions, resembling a crescent or sickle. These rigid, sickle-shaped red blood cells have trouble flowing through blood vessels, potentially causing blockages in capillaries, reducing blood flow, and leading to pain, tissue damage, and severe complications in various organs.


On the other hand, beta-thalassemia results from mutations in the beta-globin gene, one of the hemoglobin chains. These mutations can lead to reduced hemoglobin production or the production of abnormal hemoglobin. The severity of the disease can vary from asymptomatic forms to severe cases that require regular blood transfusions.


 

Casgevy, the innovative genetic editing therapy


This groundbreaking treatment embraces an ex vivo cellular approach, where a patient's hematopoietic stem cells undergo genetic modification using CRISPR tools. These modified cells multiply in the laboratory and are subsequently reintroduced into the patient, triggering the production of functional hemoglobin.

The CRISPR treatment involves targeted DNA modification to correct genetic mutations.

The genetic modification strategy focuses on the HBB gene, responsible for beta-globin in hemoglobin. Patients with these diseases retain another gene that produces fetal beta-globin, although it typically becomes silenced after birth. Researchers have managed to reactivate this gene in patients who don't generate adult beta-globin.


To restore the expression of fetal beta-globin, a region enhancing the BCL11A gene's activity, which represses fetal beta-globin production, is removed. While the BCL11A protein is retained for its function in the hematopoietic system, its level isn’t sufficient to halt fetal beta-globin production. This approach enables the continued production of this essential type of hemoglobin.


The approved CRISPR therapy has so far proven safe, with side effects akin to other cellular therapies, such as nausea and fever. Although new participants are not being admitted, trials continue. Monitoring the treatment is crucial to ensure its safety and effectiveness in patients.

 

The future of CRISPR therapy


Despite approval in the UK, assessments by other authorities like the European Medicines Agency and the US FDA are ongoing. The pricing of Casgevy, estimated between $1.35 and $2 million, factors in research, development, and personalized production costs, raising concerns about its availability.


Casgevy's approval marks a milestone in CRISPR-based genetic therapies. Vertex Pharmaceuticals and CRISPR Therapeutics, leaders in this field, are exploring treatments for various diseases, from diabetes to Duchenne muscular dystrophy. This advancement underscores CRISPR's role as a transformative tool in contemporary medicine.





Written by Irene Rodríguez

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