HealthDay News — For the first time, a gene therapy has prevented spontaneous bleeding in patients with hemophilia B, researchers reported in the New England Journal of Medicine and at the annual Meeting of the American Society of Hematology in San Diego.

Amit C. Nathwani, MBBCh, PhD, of University College London, and colleagues administered a peripheral vein infusion of a single dose of adenovirus-associated virus (AAV) vector serotype 8 that expressed factor IX (FIX) to six patients with hemophilia B who participated in the small study.

Patients were assigned to one of three dose cohorts — two patients each were assigned to a low-dose (2x1011 viral particles per kilogram of body weight), an intermediate-dose (three-times the low dose) or a high-dose (10-times the low dose). The vector was administered without immunosuppression, after which participants were followed for six to 16 months.

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Among all participants, AAV-mediated expression of FIX was observed at 2% to 1% of normal. Patients in the low-dose group, who were the first to be treated, currently have stable FIX levels of about 2% of normal. One of the low-dose patients has been able to stop regular FIX prophylaxis, while the other has extended the time between doses.

The two patients in the medium-dose group have FIX levels of up to 3% of normal, with one going for long periods without prophylaxis, while the other has discontinued treatment. 

In the high-dose group, one patient had FIX levels that peaked at 7% of normal before dropping to about 3% after experiencing liver enzyme elevation of unknown etiology that was about five times the upper limit of normal. The patient was treated with prednisone, after which liver enzymes returned to normal levels. Although the patient did not require prophylaxis for six months after the transfer, bolus protein concentrate shots were administered after a trauma event occurred.

These findings show that gene therapy “has the potential to convert the severe bleeding phenotype into a mild form of the disease or to reverse it entirely,” according to the researchers.

In an accompanying editorial Katherine Ponder, MD, of Washington University School of Medicine in St. Louis, said the trial was a “truly a landmark study, since it is the first to achieve long-term expression of a blood protein at therapeutically relevant levels.”

Both the researchers and Ponder were cautiously optimistic, as more research is needed to better understand the risks and benefits of the therapy. Several of the study researchers disclosed financial relationships with Amsterdam Molecular Therapeutics, which specializes in gene therapy.

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