Haematopoietic Stem Cell Based Gene Therapy as a Strategy to Treat Autoimmune Disease

Autoimmune diseases affect 5-6% of the Caucasian population and represent a major burden on an individual’s life-style and the nation’s health budget. There have been no cures described with current treatment based on replacement therapy and/or broad immunosuppressive agents. A challenge for research in this field is to devise strategies aimed at specifically abrogating the immune response to self-antigens while retaining an immune system that can combat foreign pathogens. The ability of the bone marrow compartment to confer immunological tolerance to a recipient is well established and the use of allogeneic and autologous haematopoietic stem cell transplantation (HSCT) to treat autoimmune disease have been reported for a number of autoimmune diseases. Results vary between trials and diseases. A critical observation is the significant rate of relapses with autologous HSCT in humans with autoimmune disease that suggest that this may not be a curative strategy. However, the ability to easily harvest autologous haematopoietic stem cells and genetically manipulate them, opens up avenues that can be evaluated in the quest to enhance HSCT as a curative strategy. The use of gene therapy to target autoantigen to HSCs in the autoimmune diseases to establish molecular chimeras and antigen-specific tolerance is still in its infancy. Nonetheless, the few experimental studies that have directly used this approach, coupled with approaches to clear the periphery of self-reactive T cells indicates that genetically-engineered HSCT may be a feasible and viable option for the curative treatment of the autoimmune diseases. _____________________________________________________________________________________________________________