Investigators at the University of North Carolina (UNC) School of Medicine and Medical College of Wisconsin (MCW) developed a gene therapy approach that uses platelets, avoiding the kind of antibody response (inhibitors) that can neutralize an infused factor therapy. The study, "Platelet-targeted Gene Therapy with Human Factor VIII Establishes Haemostasis in Dogs with Haemophilia A," was published November 2013 in the journal Nature Communications. The lead author of the study was David A. Wilcox, PhD, Department of Pediatrics in MCW.
The study was funded by the National Institutes of Health, the American Heart Association, the National Gene Vector Biorepository, and through gifts from the Children's Hospital Foundation, the Midwest Athletes Against Childhood Cancer, Inc. (MACC Fund), and John B. and Judith Gardetto.
Wilcox and his colleagues first isolated targeted platelet precursor cells (cells in the bone marrow that are incapable of self-renewal) from three dogs with hemophilia A, then engineered the cells to carry genetic material that triggered the production of factor VIII (FVIII). They then transferred the gene therapy to the dogs, which generated new platelet cells that produced FVIII.
"The promise and the hope for gene therapy is that people with hemophilia would be given a single therapeutic injection and then would express the protein they are missing for an extended period of time, ideally for years or even their entire lifetimes," said study coauthor Tim Nichols, MD, director of the Francis Owen Blood Research Laboratory at UNC.
Because platelets naturally travel to the site of bleeding, where they discharge their contents, including the FVIII, the dogs experienced enhanced clotting capacity. Two and a half years after the initial delivery of the gene therapy, investigators report that the platelets continued to be a potent manufacturer of FVIII in the three dogs, all of which exhibited lower bleeding rates. Prior to the therapy, the dogs experienced 5 serious bleeding events yearly. The dog with the highest FVIII levels had only one serious bleeding event each of the three study years, effectively treated with existing factor therapies.
"The absence of inhibitory antibodies to platelet-derived FVIII indicates that this approach may have benefit in patients who reject FVIII replacement therapies. Thus, platelet FVIII may provide effective long-term control of bleeding in patients with haemophilia A," concluded the authors.
Although promising, additional studies will be needed before this type of therapy becomes a clinical reality in humans.
Source: UNC at Chapel Hill news release dated December 11, 2013
