Indian scientists develop novel gene therapy for haemophilia

Context: Scientists in India have reported success with using gene therapy to
treat severe haemophilia A, a rare hereditary condition resulting from a faulty
gene which triggers severe, spontaneous, and potentially fatal bleeding
episodes. The results of the study were reported in the peer-reviewed New
England Journal of Medicine (NEJM) earlier this week. The trial was led by
Alok Srivastava of the Centre for Stem Cell Research (CSCR) at the Christian
Medical College in Vellore, and financially supported by the Union Department
of Biotechnology. Though only tested on five patients in Tamil Nadu so far,
none of them have reported bleeding episodes over an average follow-up period
of 14 months.

Key points

·       Overview: The trials
involved deploying a novel technology of using a lentiviral vector to express a
FVIII transgene in the patient’s own haematopoietic stem cell which will then
express FVIII from specific differentiated blood cells.

·       Haemophilia: Haemophilia is
caused by a defect in the X chromosome. Britain’s Queen Victoria (1819-1901) is
the world’s most widely known carrier of haemophilia. Haemophilia is a medical
condition, mostly inherited, in which the ability of blood to clot is severely
reduced so that even a minor injury can cause severe bleeding.

Types - The most common
type of Haemophilia is called Haemophilia A. Here, the person does not have
enough clotting factor VIII. Haemophilia B is less common. Here, a person does
not have enough factor IX.

·       Haemophilia
A: Haemophilia A, also known as classical haemophilia, is a rare and
genetic bleeding disorder caused by insufficient levels of a blood protein
called factor VIII. Factor VIII is a clotting factor (an essential protein
required for blood to clot and stop bleeding).

Caused by - Haemophilia A
is caused by disruptions or changes (variants or mutations) to the F8 gene
located on the X chromosome.

Susceptible - Haemophilia A
is mostly expressed in males but some females who carry the gene variant may
have mild or, rarely, severe symptoms of bleeding.

Statistics In
India - Haemophilia A occurs in about 1 in 5,000 births, while Haemophilia B is
even rarer at about 1 in about 20,000 births.

·       Gene
Therapy for Haemophilia: It is based on the transfer of a non-pathogenic and
non-replicating recombinant adeno-associated virus (AAV), the viral DNA of
which has been replaced by a bioengineered gene cassette, with a
tissue-specific promoter and other regulatory elements. Roctavian is the first
gene therapy to treat haemophilia A. The active substance in Roctavian,
valoctocogene roxaparvovec, is based on a virus (adeno-associated virus or AAV)
which has been modified to not cause disease in humans.

·       Conclusion: The new
approach is safer than using an adenovirus, and potentially opens the gene
therapy treatment to children. This ground-breaking study is notable for
several reasons. First and foremost, it establishes that initiating and
executing studies involving new gene therapy is possible even in
resource-constrained settings such as India.