Gene Therapy Breakthrough: A One-Time Solution for Haemophilia A

Gene Therapy Breakthrough: A One-Time Solution for Haemophilia A

Sub : Sci

Sec: Space sector

Why in News

• Indian scientists have achieved a significant breakthrough in developing a novel gene therapy for treating severe Haemophilia A. This therapy, reported in the prestigious New England Journal of Medicine (NEJM), demonstrates promising results as a potential one-time treatment for a condition that currently requires lifelong management.

What is Haemophilia A?

• Haemophilia A is a hereditary disorder caused by a faulty gene, leading to insufficient levels of clotting factor VIII in the blood.
• It triggers severe, spontaneous, and potentially life-threatening bleeding episodes.
• The severity of the condition depends on the percentage of clotting factor present:
• Severe Haemophilia A: Clotting factor <1%.
• India has the world’s second-largest pool of Haemophilia patients, with an estimated 40,000 to 1,00,000 individuals.

Types of Haemophilia:

Congenital haemophilia: Haemophilia is usually inherited, meaning a person is born with the disorder (congenital).

• Congenital haemophilia is classified by the type of clotting factor that’s low.
• The most common type is haemophilia A, associated with a low level of factor 8 The next most common type ishaemophilia B, associated with a low level of factor 9.

Acquired haemophiliac: Some people develop haemophilia with no family history of the disorder. 

• This is called acquired haemophilia.
• Acquired haemophilia is a variety of the condition that occurs when a person’s immune system attacks clotting factor 8 or 9 in the blood. 

Haemophilia inheritance: In the most common types of haemophilia, the faulty gene is located on the X chromosome. Everyone has two sex chromosomes, one from each parent. 

• Females inherit an X chromosome from the mother and an X chromosome from the father. Males inherit an X chromosome from the mother and a Y chromosome from the father.
• This means that haemophilia almost always occurs in boys and is passed from mother to son through one of the mother’s genes.

About Factor VIII:

• Factor VIII is a protein essential for blood clotting (coagulation).
• It activates Factor X in the coagulation cascade, which helps form a fibrin clot to stop bleeding.
• Blood Clotting Process:
  • When a blood vessel is injured, clotting factors work in a sequence to stop blood loss:
    • Platelets form a temporary plug at the site.
    • Clotting factors, including Factor VIII, activate to strengthen the plug by forming a fibrin mesh.
  • Role of Factor VIII: Acts as a cofactor for Factor IX to activate Factor X. Essential for converting prothrombin to thrombin, which turns fibrinogen into fibrin (a stable clot).
  • Deficiency of Factor VIII: Leads to Haemophilia A, a genetic disorder characterized by prolonged bleeding.

Indian Gene Therapy for Haemophilia A:

• Indian scientists have developed a novel gene therapy to treat severe Haemophilia A, providing a potential one-time solution for a condition that currently requires frequent treatments.
• Mechanism: A functional gene is introduced into the patient’s body. This gene enables the body to produce sufficient Factor VIII, a blood-clotting protein, to prevent bleeding episodes.
• Outcome: No bleeding episodes reported during the trial.
• Significance: Marks a safer approach compared to traditional adenovirus-based methods, potentially suitable for children.

About Roctavian:

• Roctavian is the first gene therapy approved by the S. FDA (2023) for treating severe Haemophilia A.
• It offers a one-time treatment by addressing the genetic cause of the condition.
• Mechanism: A functional copy of the Factor VIII gene is delivered into the patient’s liver cells using an Adeno-Associated Virus (AAV) vector.
• This enables the liver to produce sufficient Factor VIII, reducing or eliminating the need for regular clotting factor injections.
• Significance: Roctavian demonstrated a high efficacy rate in managing severe Haemophilia A.