Investigators report no evidence of toxicity in the four hemophilia B patients enrolled to date in a gene therapy trial using a vector under development at St. Jude Children's Research Hospital and UCL (University College London) to correct the inherited bleeding disorder.
This trial was designed primarily as a safety test, with low and intermediate doses of the vector expected to produce little detectable Factor IX. The Factor IX protein helps the blood form clots. Individual with hemophilia B lack adequate levels of this clotting factor. The first participant in the open-label Phase I/II trial had an unexpectedly high level of Factor IX expression after receiving the lowest dose of the vector being tested in this study. Levels of the Factor IX protein rose from less than 1 percent to 2 percent of normal after the experimental vector was infused into the patient.
The patient's Factor IX production remains elevated more than nine months later. Since the infusion the patient has also not suffered any spontaneous joint bleeds or needed prophylactic treatment.
Study data was presented at the 52nd Annual Meeting of the American Society of Hematology (ASH) by Amit Nathwani, M.D., Ph.D., UCL Department of Hematology, and National Health Service Blood and Transplant, UK, the study's first author. Andrew Davidoff, M.D., chair of the St. Jude Department of Surgery, is the senior author.
Work on the vector began more than 10 years ago in the St. Jude laboratory of Arthur Nienhuis, M.D., member of the Department of Hematology and a study co-author. The collaboration continued after Nathwani returned to London.
The trial vector was made by packaging a codon-optimized version of the Factor IX gene into a member of the adeno-associated virus (AAV) family known as AAV8. AAV8 was picked because the incidence of natural infection with AAV8 is low and, like other AAVs, targets liver cells but does not integrate into the patient's
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St. Jude Children's Research Hospital