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• W2345376321 abstract "Introduction The treatment of heart failure is entering a new era with the potential for gene therapy to directly target the underlying molecular abnormalities of the failing myocyte. One barrier to delivering gene therapy is the exclusion of patients who have neutralising antibodies (nAbs) to the recombinant viral vector due to previous exposure to the wild type virus. Aims To review the prevalence of nAbs against adeno-associated virus serotype 1 (AAV1) in published literature and to prospectively determine the prevalence of nAbs in a UK cohort of heart failure patients. Methods We reviewed the literature using the following search terms on Pubmed: (prevalence, neutralising antibodies, adeno-associated virus, AAV) which resulted in 19 studies. Five of these studies were suitable and provided data for 14 countries and a total of 1984 people. In addition, a total of 155 samples from heart failure patients at our institution were analysed for the presence of nAbs using a titre cut-off of 1:2. Results Globally there is a wide variation in the prevalence of nAbs to AAV1, ranging from 13 to 79%. These data are generally from young healthy volunteers and there is no standard cut-off for what titre constitutes a nAb positive result, though a titre cut-off of 1:20 was used in most of these studies. From our UK based heart failure cohort, 60.6% of patients were nAb positive at a titre of 1:2 and hence ineligible for gene therapy. The only characteristic associated with being nAb positive was age with the prevalence of nAbs increasing significantly with age (Table 1). Conclusion If gene therapy proves to be an effective treatment, then currently three-fifths of heart failure patients in the UK may be ineligible to receive it due to presence of nAbs. This barrier seems to be greater in the older patients. Published data on the prevalence of nAbs does, however, suggest there is a wide geographic variation. Strategies are in development to overcome the barrier of nAbs but until these are effective we must be conscious of this limitation when discussing gene therapy as either a research or therapeutic option with our patients in the UK." @default.
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• W2345376321 date "2015-06-01" @default.
• W2345376321 modified "2023-09-23" @default.
• W2345376321 title "41 Gene Therapy for Heart Failure: The Challenge of Neutralising Antibodies: Abstract 41 Table 1" @default.
• W2345376321 doi "https://doi.org/10.1136/heartjnl-2015-308066.41" @default.
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