CASGEVY – A GENE THERAPY

TAG: GS 3: SCIENCE AND TECHNOLOGY

THE CONTEXT:  The UK drug regulator recently approved a gene therapy called Casgevy for the treatment of sickle cell disease and thalassaemia which is seen as a groundbreaking advancement in the field of medicine.

SIGNIFICANCE OF GENE THERAPY:

• Revolutionary Treatment Approach:
  • Casgevy, utilizing CRISPR-Cas9 gene editing technology, targets and edits the faulty gene responsible for sickle cell disease and thalassemia.
  • This therapy presents a potential cure by editing the patient’s own blood stem cells to produce fetal hemoglobin, alleviating symptoms and potentially offering a lifelong remedy.
• Disease Background:
  • Sickle cell disease causes red blood cells to adopt a crescent shape, obstructing blood flow and leading to severe pain, infections, anemia, and stroke.
  • Thalassemia results in low hemoglobin levels, causing fatigue, shortness of breath, irregular heartbeats, and necessitating lifelong blood transfusions.

WORKING MECHANISM OF CASGEVY:

• CRISPR-Cas9 Gene Editing:
  • Casgevy targets the BCL11A gene, critical in the switch from fetal to adult hemoglobin.
  • By promoting the production of fetal hemoglobin (which lacks the abnormalities of adult hemoglobin), the therapy aims to alleviate symptoms of these blood disorders.

IMPACT AND TRIAL RESULTS:

• Clinical Trial Outcomes:
  • Trials involving Casgevy showcased promising results:
    • For sickle cell disease, most participants experienced a significant reduction in severe pain crises post-treatment.
    • In thalassemia, a substantial number of patients didn’t require transfusions for at least a year after treatment.

TREATMENT PROCESS:

• Treatment Procedure:
  • The therapy involves collecting the patient’s blood stem cells, editing them over six months, and then transplanting them back after conditioning the bone marrow.
  • Patients need hospitalization for about a month post-transplant to allow the edited cells to regenerate red blood cells with normal hemoglobin.
• Side Effects and Challenges:
  • Similar to autologous stem cell transplants, patients might experience side effects like nausea, fatigue, fever, and an increased infection risk.
  • The primary challenges revolve around the therapy’s high cost (possibly up to $2 million per patient) and the absence of local manufacturing facilities, making it difficult for poorer countries to afford and access the treatment.

FUTURE PROSPECTS AND CHALLENGES:

• Cost and Access:
  • While the approval signifies a significant milestone, the exorbitant cost poses a major challenge, especially for patients in lower-income countries.
  • Anticipated reductions in prices over time and the development of local manufacturing facilities may improve accessibility.
• Ongoing Research:
  • Researchers, like Dr. Debojyoti Chakraborty’s team, are actively working on similar gene therapies in India, aiming to address sickle cell disease with a focus on making the treatment more accessible.

CONCLUSION:

• The approval of Casgevy in the UK represents a momentous leap in the treatment of sickle cell disease and thalassemia, offering a potentially curative approach through gene editing technology.
• However, the high cost and accessibility issues underscore the need for ongoing research, development of local manufacturing facilities, and efforts to make such revolutionary treatments more affordable and globally accessible.

SOURCE: https://indianexpress.com/article/explained/explained-health/sickle-cell-breakthrough-9041297/