Haemophilia, a hereditary, haemorrhagic disease, is caused by the mutations in the blood coagulation factor VIII (FVIII) or IX (FIX) genes. Severe haemophilia has transformed from an incapacitating disease to a condition that allows people to live a normal life, provided that patients are diagnosed early, and also receive prophylactic therapy.
The recent advancements in coagulation factor concentrates, including recombinant preparations, have led to a better control of bleeding, and have considerably improved patient prognosis. Also, the use of prophylactic injections of a coagulation factor preparation (regular replacement therapy) prevents haemophilic arthropathy, if started in childhood.
These advances have dramatically improved the quality of life of patients with haemophilia. However, there still exist a number of challenges for people with the disease, such as infusion demands and the development of inhibitors.
The costs associated with lifelong prophylactic therapy and the risk of bleeding in between infusions has encouraged the development of gene therapy. Gene therapy is a single treatment with everlasting therapeutic effects. It can resolve the current difficulties associated with haemophilia.
Gene therapy could therefore become a cost-effective alternative. It often encompasses the use of viral vectors because of their high efficiency in transducing a target gene. The current gene therapy model for haemophilia is mainly to leave the abnormal somatic gene as it is and ectopically express a normal gene by a vector.
Gene therapy trials for haemophilia B have mostly been successful. But, the scenario has not been the same for haemophilia A — until recent clinical trials at Barts Health NHS Trust and Queen Mary University of London. Researchers found that a single treatment of haemophilia A patients with a gene therapy drug for over one year led to normal levels of the previously missing protein, and effectively cured the disease. The trial was conducted on European patients.
A single infusion of the gene therapy drug increased the levels of the essential blood clotting protein Factor VIII. A total of 85 percent of the patients (11 of 13) had normal or near-normal levels of Factor VIII even after 19 months of treatment. All the patients were able to halt their previous regular treatment.
The major areas of concern in this trial are the development of an immune response to the drug, which could be managed with steroids and immunosuppressants, and the durability of the drug. Researchers are still hopeful as the only other haemophilia trial done on humans, seven years ago, has continued to show stability. It is an incredible transformation in the treatment of haemophilia A as just a single dose dramatically improves the quality of life. Currently, patients have to frequently inject themselves. The research team involved has to carry out further tests on participants around the world, including patients in the US, Europe, Africa, and South America. These life-changing results have a particular implication as the first successful gene therapy trial for haemophilia A.
Gene therapy is always a prudent and effective mode of treatment for haemophilia because the introduction of even small amounts of the deficient protein can improve the bleeding phenotype (which was proven in the clinical trial). These positive results are encouraging and are a ray of hope for haemophilia A patients. It is a welcome change that has long been awaited.