Research Breakthrough in Gene Therapy for Hemophilia B

Horizons in Hemophilia, December 2011

Submitted by The National Hemophilia Foundation

Researchers from the United Kingdom (UK) and the U.S. have made a breakthrough in hemophilia gene therapy. In a recently published study, the team reported successfully treating six patients with severe hemophilia B. The lead author of the study was Amit C. Nathwani, MB, ChB, PhD, Department of Hematology, University College London (UCL) Cancer Institute, London.

The UCL investigators used adeno-associated viruses (AAVs) as delivery vehicles, or vectors, to carry the genetic codes that trigger the production of the factor IX (FIX) protein. FIX is deficient in hemophilia B patients. Ideally, AAVs deliver the genetic material into living cells to sustain therapeutic effect without causing disease or triggering significant immune responses.

Nathwani and his team reported that a single injection of the gene therapy activated the production of small amounts of FIX--enough to allow four of the six subjects to cease treatment with FIX concentrates. The other two patients continued treatment with factor products but needed less frequent infusions. The patients have continued to produce their own FIX for up to 22 months.

Over the last decade, one of the major focuses for researchers has been on developing optimal AAVs. These viruses are often favored because patients have little or no immunity to them. Further, AAVs often target liver cells, which manufacture FIX. One potential drawback is long-term viability as liver cells to do not live indefinitely and are slow to regenerate, which may affect the duration of the therapy.

The AAVs for this study were prepared by a team from the St. Jude Children’s Research Hospital in Memphis, TN. The patients were recruited and treated with the therapy by investigators at UCL. Study co-author Katherine High, MD, and fellow researchers at the Children’s Hospital of Philadelphia, are monitoring the study for any immune reactions.

High’s laboratory has been conducting gene therapy clinical trials for hemophilia for more than a decade. “I think it’s incredibly exciting, and I say that even though these people are my competitors,” said High.

According to Edward G.D. Tuddenham, MB, BS, MD, director of the Hemophilia Center at the Royal Free Hospital in London, 20 additional patients will receive the therapy to help determine the optimal dose of the AAV. The aim is to deliver the highest possible dose while circumventing an unwanted immune response. “We are pretty close to the sweet spot,” explained Tuddenham. “If all goes well, a genetic treatment for hemophilia B could be available for widespread use in a couple of years.”

The study, “Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B,” was published online on December 10, 2011, by The New England Journal of Medicine.

Source: The New York Times, December 10, 2011