Gene Therapy Offers New Hope for Hemophilia
Gene therapy, a technique for correcting faulty genes, found to offer a new hope for patients suffering from blood clotting disorder like hemophilia B.
According to the findings of Phase I study issued in the online edition of the New England Journal of Medicine, gene therapy can reduce spontaneous bleeding episodes in patients with the inherited bleeding disorder. Researchers at St. Jude Children’s Research Hospital in Memphis developed a gene therapy that successfully treated six patients with severe haemophilia B, characterised by defect in blood clotting mechanism.
Hemophilia B is a hereditary bleeding disorder caused by mutation in the gene for producing a protein called Factor IX or Christmas factor, which is essential for normal blood clotting. Disease occurs solely in men, as the factor IX gene is carried on the X chromosome of which men have only a single copy (XY pattern). The defective gene is inherited by at least 1 in 30,000 individuals. Hemophilia B can turn out fatal if left untreated, as patient bleed spontaneously following trauma.
Previous gene therapies for hemophilia B by inserting a right copy of the gene failed to improve blood-clotting for longer duration.
To confirm safety and efficacy of new gene therapy, researchers conducted a clinical trial at the University College London (UCL) in the U.K. They treated six men with severe hemophilia B with adeno-associated virus (AAV) 8 mediated gene transfer therapy.
The six trial participants were divided into three groups with each group getting a various concentration of new genes. Each of them received a single, 20-minute infusion of the Factor IX gene and additional genetic material into a vein in the arm. Adeno-associated virus (AAV) 8, as a vector, delivered genetic material into liver cells, cells able to produce clotting factors VIII and IX. Selected viruses did not cause disease in recipients.
In each man the amount of factor IX in his blood increased from less than 1 percent of normal levels to at least 2 percent, and in one case as much as 11 percent.
Four out of six study participants gave up routine protein injection to avoid bleeding episodes after receiving the therapy and were exempted from spontaneous bleeding.Remaining two exhibited increased time interval between two subsequent factor IX injections indicating increasing blood clotting ability.
According to researchers, in first patient the amount of factor IX levels remained at 2 percent for more than 18 months during follow-up .The two patients who were treated with the highest dose have seen FIX levels rise to between 3 and 12 percent. Of the two participants who received high-dose of vector, one showed elevated levels of transaminases, signalling possible liver damage, and another had a slight rise in liver enzymes. Both cases were resolved with steroids.
Dr. Amit Nathwani, M.D., Ph.D., a faculty member at the UCL Cancer Institute, Royal Free Hospital and NHS Blood and Transplant (NHSBT) said:
“This is a potentially life-changing treatment for patients with this disease and an important milestone for the field of gene therapy. It could have ramifications for the treatment of hemophilia A, other protein and liver disorders and chronic diseases such as cystic fibrosis.”
Treatments of hemophilics with infusion of factor IX protein can annually cost $50,000 for a child and more than $150,000 in most severe patients. But the single required injection of the new gene therapy costs $30,000 only. This can be satisfying news for patients.
Researchers believe that additional clinical trials are required to confirm safety and effectiveness of new gene therapy. Respective gene therapy can bring substantial betterment in the quality of life of haemophilic patient. But procedure may seem to be difficult to carry out in practice as immune response against virus may develop before gene is accepted by liver cells. Hence, it will take some more time to make gene therapy available to most of the patients.