Peer-reviewed veterinary case report
Long-term gene therapy helps dogs with severe hemophilia
By Sabatino, Denise E et al.·Published in Molecular therapy : the journal of the American Society of Gene Therapy·2011·Department of Genetics, United States·View original on PubMed →
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Original publication title: Efficacy and safety of long-term prophylaxis in severe hemophilia A dogs following liver gene therapy using AAV vectors.
- Species:
- dog
Plain-English summary
A group of dogs with severe hemophilia A (a bleeding disorder) received gene therapy to help their bodies produce a missing protein that prevents bleeding. The treatment involved delivering a gene using a special virus, and it was found to be safe and effective. Over time, the dogs showed a significant reduction in bleeding episodes, with more than 90% fewer incidents reported. This promising outcome suggests that gene therapy could be a viable long-term solution for managing hemophilia A in dogs.
People also search for: dog hemophilia A treatment · gene therapy for dogs · bleeding disorder in dogs
Abstract
Developing adeno-associated viral (AAV)-mediated gene therapy for hemophilia A (HA) has been challenging due to the large size of the factor VIII (FVIII) complementary DNA and the concern for the development of inhibitory antibodies to FVIII in HA patients. Here, we perform a systematic study in HA dogs by delivering a canine FVIII (cFVIII) transgene either as a single chain or two chains in an AAV vector. An optimized cFVIII single chain delivered using AAV serotype 8 (AAV8) by peripheral vein injection resulted in a dose-response with sustained expression of FVIII up to 7% (n = 4). Five HA dogs administered two-chain delivery using either AAV8 or AAV9 via the portal vein expressed long-term, vector dose-dependent levels of FVIII activity (up to 10%). In the two-chain approach, circulating cFVIII antigen levels were more than fivefold higher than activity. Notably, no long-term immune response to FVIII was observed in any of the dogs (1/9 dogs had a transient inhibitor). Long-term follow-up of the dogs showed a remarkable reduction (>90%) of bleeding episodes in a combined total of 24 years of observation. These data demonstrate that both approaches are safe and achieve dose-dependent therapeutic levels of FVIII expression, which supports translational studies of AAV-mediated delivery for HA.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/21081906/