Researchers at the Christian Medical College, Vellore have used gene therapy to treat severe haemophilia A, an inherited condition leading to severe bleeding due to a defective gene.
Usual Treatment for Haemophilia:
Replacement Therapy:
Involves injecting clotting factor concentrates (Factor VIII for haemophilia A and Factor IX for haemophilia B) to control bleeding.
Clotting factors can be derived from human blood or recombinant sources to minimize disease transmission risks.
Recombinant clotting factors allow at-home use and reduce risks associated with human blood.
Desmopressin (DDAVP) is used for mild haemophilia A but not for severe cases or haemophilia B.
Challenges:
Antibodies can destroy the clotting factor before it works, complicating treatment.
Gene Therapy for Haemophilia:
Introduces a corrected gene into cells, aiming for normal expression of the clotting factor.
FDA-Approved Therapy:
Roctavian (approved in 2023): Uses an adeno-associated virus (AAV) to carry the gene for Factor VIII to liver cells.
Clinical results showed a reduction in annual bleeding rates from 5.4 to 2.6 bleeds per year.
Corticosteroids often accompany Roctavian to suppress immune responses.
Effectiveness may decline over time.
Differences in the Vellore Trial:
Vector Choice:
Used a lentivirus instead of an adenovirus.
This is significant because fewer people have antibodies against lentiviruses, enhancing effectiveness.
Gene Transfer Approach:
Involves gene transfer into adult stem cells using a lentiviral vector that integrates with body cells.
Expected benefit: Long-term clotting factor production without side-effects.
Trial success: Five patients in Vellore had no bleeding episodes over 14 months.
Treating a haemophiliac in India costs approximately $300,000 over 10 years.
There are about 100,000 haemophiliacs in India, predominantly Type A.
Roctavian costs around $2 million, making affordability challenging.
The Vellore gene-therapy product aims to be more cost-effective.
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