Casgevy Therapy for Sickle Cell Disease and Thalassaemia | 30 Nov 2023

Source: IE

Why in News?

Recently, the UK Drug Regulator sanctioned a gene therapy called Casgevy heralded as a significant breakthrough for treating sickle cell disease and thalassaemia.

• Notably, this marks the world's inaugural licensed therapy leveraging the CRISPR-Cas9 gene editing technology that earned its innovators a Nobel Prize in Chemistry 2020.

How does the Casgevy Therapy Work?

• Both sickle cell disease and thalassaemia are caused by errors in the gene for haemoglobin(Hb), a protein in the red blood cells that carry oxygen to organs and tissues.
  • The therapy uses the patient’s own blood stem cells, which are precisely edited using CRISPR-Cas9.
  • A gene called BCL11A, which is crucial for switching from foetal to adult haemoglobin, is targeted by the therapy.
• Foetal haemoglobin, which is naturally present in everyone at birth, does not carry the same abnormalities as adult haemoglobin.
  • The therapy uses the body’s own mechanisms to start producing more of this foetal haemoglobin, alleviating the symptoms of the two conditions.
• Casgevy involves a single treatment wherein blood stem cells are extracted via apheresis and then edited over approximately six months before being reintroduced into the patient.
  • Apheresis is a medical procedure that involves removing specific components from blood and returning the rest to the body.

What are Sickle Cell Disease and Thalassaemia?

• Sickle Cell Disease:
  • About: Sickle cell disease is a genetic blood disorder characterized by an abnormality in hemoglobin, the protein responsible for carrying oxygen in red blood cells.
    • It causes red blood cells to adopt a sickle or crescent shape, hindering their movement through vessels, leading to potential complications like severe pain, infections, anaemia, and strokes.
    • In India alone, an estimated 30,000-40,000 children are born with sickle cell disease annually.
  • Types: It encompasses various types, each dependent on the inherited genes from parents, all encoding abnormal hemoglobin. The most prevalent forms of SCD include:
    • HbSS (Sickle Cell Anemia): Individuals inherit two "S" genes, one from each parent, resulting in abnormal hemoglobin "S."
      • This type often leads to severe manifestations characterized by rigid, sickle-shaped red blood cells.
    • HbSC: Inheriting an "S" gene from one parent and a different abnormal hemoglobin, "C," from the other, leads to this milder variant of SCD.
    • HbS Beta Thalassemia: This form arises from inheriting an "S" gene from one parent and a beta thalassemia gene from the other.
      • The severity varies based on the type of beta thalassemia inherited either "zero" (HbS beta0) or "plus" (HbS beta+), with the former typically resulting in a severe form and the latter in a milder manifestation.
• Thalassaemia: Similar to sickle cell disease, individuals with thalassaemia experience severe anaemia due to low haemoglobin levels, necessitating lifelong blood transfusions and chelation therapy to manage iron accumulation.
• Major symptoms include fatigue, paleness or jaundice, shortness of breath, delayed growth, facial bone deformities (in severe cases) among others.