Cell and Gene Therapies
Researching a Treatment for Hemophilia
There is currently no cure for the rare bleeding disorder hemophilia. Because people with hemophilia have little or no clotting factor, a protein needed for normal blood clotting, they may bleed for a longer time than others after an injury, as well as bleed internally, especially in joints such as the knees, ankles, and elbows. This bleeding can damage the organs and tissues and be life threatening.
People with hemophilia A, the most common type, are missing clotting factor VIII. Institute researchers are exploring the possibility of treating the disorder with gene therapy. Their strategy is to engineer mesenchymal stem cells, a type of adult stem cell, so that they produce high levels of factor VIII. The cells – acting as a carrier for the gene – would then be transplanted into the patient.
Being able to cure hemophilia with stem cell transplants would be significant. The current treatment for severe cases is regular injections of clotting factor. However, a majority of patients in the world with the disorder don’t’ have access to this treatment, which costs $400,000 per year. In addition, about a third of patients develop antibodies to the treatment. The researchers hope that if their approach isn’t successful at curing the disease, it would at least solve the antibody problem so that current treatment would be effective.
In an animal model of hemophilia, the researchers used stem cells from the father’s bone marrow, which they engineered to produce high levels of factor VIII. Mesenchymal stem cells were selected because they have the ability to home to sites of injury or inflammation. In two treated animals, the cells migrated to the joints and stopped ongoing bleeding. Perhaps even more impressive, all spontaneous bleeding events ceased, and the existing joint damage was completely reversed, restoring normal posture and gait to these crippled animals, and enabling them to resume a normal activity level.
Currently, the scientists are working to find better ways of administering cells and also to understand a paradox of the treatment – while the stem cells were able to stop the bleeding, the treatment induced an immune response in the animals.
A project to develop a gene therapy for myotubular myopathy may one day benefit children born with this often fatal genetic disease.