The long-awaited announcement came on December 8th, revealing that the US Food and Drug Administration (FDA) had given the green light to two gene therapies for sickle cell disease. This milestone includes the groundbreaking approval of the first CRISPR-based treatment for any disorder. The treatments, known as exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovocel), are now authorized for individuals aged 12 years and older who have a history of vaso-occlusive events.

For individuals with sickle cell disease, these genetic therapies offer hope for transformation, particularly as the disease disproportionately affects Black individuals, who have historically faced neglect and discrimination. This approval marks a significant achievement for both science and medicine, arriving just over a decade after the initial discovery of CRISPR.

However, significant hurdles remain on the path to realizing a cure for sickle cell disease for all patients. The disorder affects an estimated 7.7 million people globally, causing chronic and debilitating symptoms such as severe pain, organ damage, and a reduced quality of life. Compared to the general population, those with sickle cell disease also have a shorter life expectancy.

While stem cell transplants from matched donors remain the only proven cure, the procedure carries high morbidity rates, and a shortage of donors restricts its availability. The newly approved therapies involve a process of extracting, genetically modifying, and reintroducing the patient’s own hematopoietic stem cells. Lovocel utilizes a conventional approach, employing a lentiviral vector to deliver a modified β-globin gene into the cells. In contrast, exa-cel utilizes CRISPR technology to deactivate the BCL11A gene, thereby restarting the production of normal fetal hemoglobin and inhibiting the polymerization of sickled hemoglobin.

Read more here.

References

  1. The Lancet. The promise of genetic therapies in sickle cell disease. Lancet. 2023 Dec 16;402(10419):2265. doi: 10.1016/S0140-6736(23)02797-6. PMID: 38103934.

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