Why in News?

Indian scientists have achieved a major milestone by using gene therapy to treat severe Hemophilia A, a rare genetic condition causing life-threatening bleeding episodes. This pioneering work, tested on five patients in Tamil Nadu, has shown promising results, with no bleeding episodes reported over an average follow-up period of 14 months.

What’s in Today’s Article?

• What is Gene Therapy?
• Understanding Hemophilia A
• The Promise of Gene Therapy
• Global Context of Gene Therapy
• Significance of the Gene Therapy Success in India
• Conclusion

What is Gene Therapy?

• Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use.
• It is used to treat or cure disease including cancer, genetic diseases, and infectious diseases.
• Gene therapies can work by several mechanisms:
  • Replacing a disease-causing gene with a healthy copy of the gene.
  • Inactivating a disease-causing gene that is not functioning properly.
  • Introducing a new or modified gene into the body to help treat a disease.
• There are a variety of types of gene therapy products, including:
  • Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
  • Viral vectors: Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
  • Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
  • Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
  • Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.

Understanding Hemophilia A:

• What is Hemophilia?
  • It is a rare, inherited blood disorder that prevents blood from clotting properly.
  • It can be classified as minor or severe depending on the percentage of clotting factors present in those afflicted.
• What is Hemophilia A?
  • Meaning: It is a rare hereditary disorder caused by the absence of Factor VIII, a critical blood-clotting protein.
  • Severity: Classified as minor or severe based on clotting factor levels; severe cases have less than 1% clotting factor.
  • Global context: India has the world’s second-largest patient pool, estimated at 40,000-100,000.
• Current treatments:
  • Frequent interventions: Repeated Factor VIII infusions, monoclonal antibodies, or mimicking substances are used.
  • High costs: Treatment costs in India are approximately ₹2.54 crore per patient over 10 years, making it inaccessible for many.

The Promise of Gene Therapy:

• How does it work?
  • One-time solution: Gene therapy introduces a functional gene that enables the body to produce sufficient Factor VIII, reducing or eliminating the need for repeated infusions.
  • Innovative technique used: The Indian trial fused stem cells with the clotting factor gene using lentivirus (a safer vector compared to adenovirus), which eliminates the need for immunosuppressive drugs.
• Results from the trial:
  • Patients: Five individuals treated, with no bleeding episodes over 14 months.
  • Research team: Led by Alok Srivastava from the Christian Medical College (CMC), Vellore.
  • Support: Funded by the Union Department of Biotechnology.

Global Context of Gene Therapy:

• Roctavian: Approved by the U.S. FDA in 2023, reducing bleeding incidents significantly in patients.
• Mechanism: Uses adenovirus vectors to deliver the therapeutic gene, requiring immune suppression.

Significance of the Gene Therapy Success in India:

• Experts called the study “ground-breaking” due to:
  • Resource constraints: Demonstrating the feasibility of conducting advanced gene therapy in a developing country.
  • Cost reduction: Potential for localising gene therapy manufacturing in India, improving accessibility.
  • Broader access: Overcoming barriers like immunosuppressive therapy and age limitations. This method may allow younger patients to receive treatment, overcoming challenges like liver maturity and health.

Conclusion:

• The success of this gene therapy trial in India represents a transformative step in treating Hemophilia A, offering a safer, more accessible, and effective solution.
• This breakthrough not only holds promise for India but also sets a global precedent for advancing medical care in resource-constrained settings.