Gene therapy corrects factor VII deficiency bleeding disorder

A single gene therapy injection successfully corrected factor VII deficiency in dogs; this result sets the stage to begin clinical trials in humans with the same rare bleeding disorder, according to an article published in the journal Blood.

“Our finding has great clinical relevance for patients with factor VII deficiency,” said study leader Paris Margaritis, DPhil, Research Assistant Professor of Pediatrics at the Raymond G. Perelman Center for Cellular and Molecular Therapeutics (CCMT) at The Children’s Hospital of Philadelphia (CHOP), in Philadelphia, PA.

“These dogs have the type of mutation found in the majority of patients with this disorder, so this approach could lead to a sustained gene therapy in people,” Dr. Margaritis said.

Factor VII (FVII) deficiency is a rare autosomal recessive disorder that occurs in about 1 in 500,000 people. Currently, acute bleeding episodes are treated by infusion of fresh-frozen plasma, plasma-derived FVII concentrates, prothrombin complex concentrates, and low-dose recombinant activated human FVII.

For this study, researchers used a single injection to deliver a canine FVII zymogen transgene within an adeno-associated viral vector into 4 dogs with the FVII mutation. The dogs are housed in a colony for hematology research at the University of North Carolina (UNC), in Chapel Hill, NC, whose researchers collaborated with the team at CHOP.

In related studies in dogs with hemophilia B, similar positive findings translated to humans with the bleeding disorder.

“For many people living in the developing world, constant injections aren’t practical or at least not feasible right now; but a single injection could be,” said study co-author Tim Nichols, MD, who led the UNC team and is Professor of Medicine and Pathology at the UNC School of Medicine.

Within 3 months of injection, the treated dogs expressed levels of clotting factor VII that would be therapeutic in humans. Results also persisted long-term; in one dog, the effects have continued nearly 3 years. The researchers also used serum markers of kidney and liver function in the dogs, which demonstrated that the treatment was safe and didn’t elicit unwanted immune responses.

“This work is very exciting and promising,” Dr. Nichols said. “Our data are the first to demonstrate feasibility, safety, and long-term duration of AAV gene therapy for factor VII deficiency. The table is now set to propose clinical trials that would treat people who suffer from this disease.”