Gene Therapy for Hemophilia A: A Major Breakthrough in India

India’s first human gene therapy for Hemophilia A was done in Chennai at the Centre for Stem Cell Research (CSCR), Christian Medical College (CMC), Vellore. Five patients who received gene therapy had zero hemorrhagic events for a longer period, which could be considered a major breakthrough. Such therapy helps patients produce Factor VIII, which means that the need for clotting factor injections is excluded. A new kind of lentiviral vector was employed to transduce the Factor VIII gene, which was more effective and less hazardous compared to other kinds of AAV vectors. The findings of this study encourage treating genetic diseases, particularly in the context of developing nations where existing therapies for these diseases are expensive and difficult to obtain. It is essential for the enhancement of the quality of life and the availability of treatment for the 1,36,000 people in India suffering from Hemophilia A. Consideration of gene therapy as a cure and treatment for hemophilia proves to be long-term and economically efficient in contrast to multiple visits to the hospital, and the high price of Factor VIII.

What is Hemophilia A? 

• About: 

  • Hemophilia is a rare bleeding disorder caused by congenital deficiency, a particular factor of blood coagulopathy. 

  • Hemophilia A is the most common. It is caused by a deficiency of a very important blood plasma factor called factor VIII. 

  • Because of this, a person has delayed hemostasis and experiences prolonged bleeding after getting injured as compared to normal. 

  • This is because blood takes much longer for hemostasis to take place as compared to normal ones. 

• Causes: 

  • It is mainly inherited (genetic) and follows an X-linked recessive pattern, meaning that the gene responsible for factor VIII production resides on the X chromosome. 

  • Males carry one X chromosome and one Y chromosome, while females carry two X chromosomes. A male who inherits an X chromosome with the defective gene from his mother will have hemophilia A. 

  • Usually, females with a single defective copy do not exhibit symptoms due to the presence of the other X chromosome usually providing sufficient factor VIII. 

  • However, hemophilia A can occur in females if they receive two defective copies, one from each parent (much less common). 

Symptoms: 

• Variations in severity of hemophilia A depend on factor VIII level activity maximum and minimum in the bloodstream. 

Common symptoms might include: 

• Excessive bruises and bleeding-with all minor injuries (i.e., cuts and scrapes) bleeding in the joint (especially knees, elbows, and ankles) which causes swelling and stiffness pain, bleeding occurring from surgery or dental procedures. 

Treatment: 

• This may be replaced by the needed blood coagulant factor so that blood can clot normally. This is usually mediated through the injection of intravenous treatment products known as clotting factor concentrates. 

• There are two major categories of available clotting factor concentrates: 

  • Plasma-derived Factor Concentrates: It is made from human plasma that is the liquid part of blood with some proteins such as clotting factors. 

  • Recombinant Factor Concentrates: The factor concentrates were initially introduced in the year 1992, they are genetically engineered 

    • Coaghed by DNA technology and do not involve human plasma. 

    • These products do not contain plasma or albumin, therefore have no capability to pass blood borne viruses. 

But gene therapy is now coming into focus.  

• In recent trials, they applied a new approach that entails placing an FVIII gene inside a virus called lentiviral vector, which is injected into the patient’s own stem cells.  

• They, in turn, release FVIII if, and only if they mature into specially designed red blood cells, white blood cells or platelets. 

Acquired Hemophilia A: Though, Hemophilia A is inherited it can develop later in life because of auto-antibodies that are formed against factor VIII. 

• Acquired hemophilia A is relatively unusual and unlike congenital hemophilia A, its onset is acquired at a later stage in life. 

Note

• World Haemophilia day is observed on 17th April every year and focuses on the global need for awareness about Hemophilia & other bleeding disorders. It is a day nominally in honor of Frank Schnabel, the founder of the World Federation of Haemophilia (WHF). 

Government initiatives:

• National Programme for Prevention and Control of Blood Disorders (NPCBD)

• Hemophilia Federation (India)

• Rashtriya Arogya Nidhi (RAN) Scheme

• Ayushman Bharat

• Free Distribution of Factor VIII

Conclusion

India’s first human gene therapy for Hemophilia A represents a major leap in treating genetic disorders, offering a cost-effective and sustainable solution. This innovation holds immense promise, especially in developing nations like India, by improving patient quality of life and reducing dependency on expensive treatments.