The partners have taken significant steps towards the realization of the aforementioned objectives by increasing the efficacy of muscle-directed gene delivery using novel engineered adeno-associated viral vectors (AAV) and by boosting muscle-targeted gene expression levels in the desired target tissues using novel transcriptional elements identified by genome-wide data-mining. Successful efforts were made to minimize undesirable immune reactions by inducing immune tolerance to the transgene products. Steps were made towards the (large-scale) manufacturing of the novel AAV vectors towards initial preclinical validation in animal models of Pompe and myotubular myopathy yielding encouraging efficacy and safety data. The seroprevalence of the new AAV capsids had also been investigated and strategies to eliminate circulating antibodies to AAV have been developed. In addition to the research per se , feedback from the regulatory authorities (European Medicine Agency) had also been obtained. Furthermore, the partners have performed active dissemination and communication activities in the form of press releases or participation in relevant events and liaising with various patient organizations. In particular, awareness for the project’s mission and vision within the scientific community has been created in particular by presenting research and networking at international conferences and meetings and dissemination via the MYOCURE website. Some of the main dissemination events were the annual congresses of the European Society for Gene and Cell Therapy and its national meetings, the American Society of Gene and Cell Therapy and various congresses with a strong focus on muscle disorders and lysosomal storage diseases. MYOCURE contributed actively to the organization of these various scientific events and organized workshops on key technological innovations in the AAV field. The dissemination efforts of the MYOCURE partners also facilitated liaising with multiple stakeholders with a specific interest in the MYOCURE program, including scientist, clinicians, regulatory exports, patients, manufacturing experts and industrial stakeholders with implications for exploitation and valorization. Finally, the MYOCURE partners published their work in peer-reviewed journals (e.g. Science Translational Medicine, Nature Communications, Journal of Clinical Investigations, Molecular Therapy, Human Gene Therapy, Gene Therapy, Molecular Therapy Clinical Development etc.). Several publications will be submitted. The realization of these dissemination objectives provides an independent objective quantitative and qualitative measure of the progress made by MYOCURE.
