Studies in various animal models have shown that direct injection of gene therapy into the liver produces long-term correction of hemophilia. However, the liver is a challenging organ to use: it is subject to damage from comorbidities such as hepatitis and repeated infusion of factor product, and is embedded deep inside the body. These limitations have led scientists to consider alternate sites to deliver gene therapy for hemophilia. A current study led by Dr. Hengjun Chao, Assistant Professor of Hematology and Medical Oncology at Mount Sinai School of Medicine in New York, is attempting to understand the feasibility of gene therapy for hemophilia B via intramuscular injection. The paper was published in the June 2007 Journal of Thrombosis and Haemostasis. Chao is the current recipient of a grant collaboratively sponsored by the National Heart, Lung, and Blood Institute and the National Hemophilia Foundation.
The advantages of injecting gene therapy into a muscle are that it is closer to the body’s surface and is biologically uncompromised by repeated factor infusion. One of the problems with gene therapy is the body’s immune response—in some people gene therapy triggers the production of inhibitors against the factor. Thus, a successful gene therapy method must ensure that the immune response from the body is tolerant to the factor IX (FIX) produced by the body.
Dr. Chao’s team was able to efficiently induce immune tolerance through intramuscularly administered gene therapy for hemophilia B by using an adeno-associated virus 1 (AAV1), a nonvirulent strain that is engineered to contain only the genes that scientists put into them. However, these results are preliminary, having only been tested in mice. Dr. Chao’s team will be further refining its study to develop this technique for use in humans.
Source: Cohn EF, Zhuo J, Kelly ME, Chao HJ. “Efficient Induction of Immune Tolerance to Coagulation Factor IX Following Direct Intramuscular Gene Transfer.” Journal of Thrombosis and Haemostasis. 2007; 5: 1227-1236.