New research shows that a CRISPR (which stands for clustered regularly interspaced short palindromic repeats) gene-editing therapy has the potential to be a one-time cure for severe sickle cell disease and transfusion-dependent beta thalassemia (TDT).
Both TDT and sickle cell disease are blood disorders caused by genetic mutations that affect hemoglobin, the molecule that carries oxygen in the blood. Conventional treatments include regular blood transfusions and, in some cases, bone marrow transplants, however finding donors is difficult and the operation can have serious complications.
Read more: Discover the history, trends, challenges and research shaping the future of CRISPR
Exa-cel (full name exagamglogene autotemcel), an investigational therapy developed by Vertex Pharmaceuticals and CRISPR Therapeutics, was given to 75 patients during Phase II clinical trials, 44 of which had TDT while 31 had sickle cell disease. The results of the study were published in 2021, and found that 42 of the 44 patients with TDT did not need blood transfusions after being administered with exa-cel for the duration of their follow-up, which lasted three years in some cases.
Patients with severe sickle cell disease experience recurrent vaso-occlusive crises, which occur when abnormal (or “sickled”) red blood cells restrict blood flow, causing tissues to become deprived of oxygen and leading to inflammation.
All 31 patients with sickle cell disease on the exa-cel trial reported no vaso-occlusive crises after treatment.
Long-term cure for blood diseases
Phase III trials are now fully enrolled, while recruitment is underway for studies to investigate the efficacy of exa-cel in children aged five to 11. If successful, it is hoped the treatment could be given to children early enough to prevent the long-term consequences of these blood diseases.
Exa-cel edits a patients’ own stem cells to produce a type of hemoglobin usually only present during fetal development. People who experience few symptoms from either TDT or sickle cell disease have been found to continue producing high levels of this hemoglobin during adulthood.
Fast track designation
Based on its progress so far, exa cel has been granted Fast Track designation from the US Food and Drug Administration (FDA) as well as Orphan Drug Designation from the European Commission.
One of the clinicians involved in the research, Franco Locatelli, M.D., Ph.D., Professor of Pediatrics at the Sapienza University of Rome, said: “The remarkable results based on this approach give me great optimism and confidence in the potential of this treatment for patients.
“I have seen first-hand the impact that this investigational therapy has had on patients in these clinical trials and continue to be impressed by the totality of the data,” he added.
Quick links
• Rewriting the human genome
• What's next for CRISPR? Cas9, Cas3 and beyond
• Keeping tabs on pharma: World’s first GMO heart transplant
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