Traditional treatment for hemophilia A requires infusion of synthetic FVIII, a blood clotting protein, two to three times a week to control bleeding episodes. However, about 30% of these patients develop antibodies to FVIII, selectively inactivating its clotting properties and negating its therapeutic role.
Treatment for adults who have these inhibitory antibodies can cost over $1 million annually if there is a major bleeding episode.
According to the study’s lead author, Dr Qizhen Shi, “Our team of scientists have developed an approach in mice that not only could make gene therapy successful for patients with hemophilia who don’t have antibodies, but more importantly can be used to treat patients with antibodies.”
“To get around the antibody attack on FVIII,” Dr Shi explained, “we inserted a gene into a blood stem cell so that FVIII is produced and stored in blood platelets, hidden from view and attack, ready to release when a blood vessel is damaged, quickly enabling normal clotting before the antibodies can begin their attack. Our approach was very effective even in mice treated with five to ten thousand times the amount of antibody that would normally prevent treatment of a hemophilia patient with FVIII.”
The new method will next be tested in larger animal models before clinical trials can begin in patients.
Blood and bone marrow stem cells would be harvested from hemophilia patients in much the same way they are collected from bone marrow donors. A non-replicative virus containing the FVIII gene would be introduced into the stem cells from the patient. The FVIII engineered for production only in platelets would insert itself into the DNA of the stem cells. These same stem cells would then be given back to the donor patient and the stem cells would continue to make blood cells normally, releasing the life-saving FVIII only when the platelets stick to a bleeding site of injury.