Indian Scientists Develop Novel Gene Therapy Treatment for Haemophilia A

1. In December 2024, Indian scientists developed a new gene therapy to treat severe haemophilia A, a rare genetic disorder that causes spontaneous and severe bleeding.
2. The trial was conducted on 5 patients in Tamil Nadu, with positive results after an average follow-up of 14 months.
3. The study was led by Alok Srivastava from the Centre for Stem Cell Research (CSCR) at Christian Medical College, Vellore, and supported by the Union Department of Biotechnology.
4. The findings were published in the New England Journal of Medicine (NEJM).

What is Haemophilia A?

1. Haemophilia A is a genetic disorder where the body lacks a clotting protein called Factor VIII, which helps blood to clot.
   1. The factor VIII (F8) gene is a large gene on the X chromosome that provides instructions for making coagulation factor VIII, a protein that helps blood to clot.
2. Without this factor, individuals with haemophilia experience spontaneous bleeding that can be severe and life-threatening.
3. Types of Haemophilia:
   1. Minor haemophilia: Low levels of clotting factor.
   2. Severe haemophilia A: Very low or almost no Factor VIII (less than 1% of normal levels).
4. Prevalence in India: Though haemophilia is rare worldwide, India has one of the largest patient groups, with about 40,000 to 100,000 patients.

Current Treatment for Haemophilia A

1. Traditional Treatment: Patients with haemophilia A usually receive regular injections of Factor VIII to prevent bleeding.
   1. Those with severe haemophilia may need weekly injections or other treatments like monoclonal antibodies to replace the missing clotting factor.
2. Challenges:
   1. The treatment is expensive. A 10-year treatment cost in India is estimated at around $300,000 (₹2.54 crore) per patient.
   2. It involves lifelong, frequent injections, making it difficult and costly for patients.

Gene Therapy Approach:

1. Gene therapy is a new way to treat haemophilia by introducing a healthy copy of the Factor VIII gene into the patient’s body.
2. This gene can then make enough Factor VIII to help blood clot.
3. Gene therapy could provide a one-time solution, reducing the need for lifelong injections.

Details of the Indian Clinical Trial

1. Trial Design: The trial was conducted on five patients from Tamil Nadu who have severe haemophilia A.
2. Results:
   1. After an average follow-up of 14 months, none of the patients had any bleeding episodes.
   2. Normally, patients with severe haemophilia experience frequent bleeding (sometimes every week), making the trial results very significant.
3. Gene Delivery Method:
   1. The gene therapy was delivered using a lentivirus vector. This method involves fusing the Factor VIII gene with the patient’s stem cells, which were then put back into their bodies.
   2. This approach is different from other gene therapies, such as Roctavian, which uses an adenovirus vector.

Comparison with Roctavian Gene Therapy

1. Roctavian is a gene therapy approved by the U.S. Food and Drug Administration (FDA) for haemophilia A.
   1. In clinical trials, Roctavian reduced bleeding episodes from 5.4 per year to 2.6 per year.
   2. However, Roctavian requires patients to take immune-suppressing drugs (corticosteroids) to prevent the body from rejecting the therapy.
   3. Roctavian uses an adenovirus vector, which involves the liver in producing Factor VIII.

2. In contrast, the Indian study:

   1. Used a lentivirus vector, which is considered safer than the adenovirus approach.
   2. It also does not require immune-suppressing drugs, making it easier and safer, especially for children.

Significance of the Indian Study

1. The study is described as "ground-breaking" because it shows that advanced gene therapy can be done even in resource-limited settings like India.
2. According to Dr. Johny Mahlangu (in an editorial in NEJM), this study proves that gene therapy research can be carried out in countries with fewer resources.
3. If this gene therapy is successful, it could help lower treatment costs by allowing local production of the therapy in India, making it more affordable.
4. The use of the lentivirus vector makes this therapy safer and more suitable for children, as it does not require immune-suppressing drugs, which are used in other treatments like Roctavian.
5. This gene therapy could help increase the global availability of treatment for haemophilia, especially in low-income countries like India.

Conclusion

The gene therapy trial in India represents a huge breakthrough in treating severe haemophilia A. The positive results from the trial provide strong evidence that gene therapy could offer a long-term, cost-effective solution for haemophilia patients.