Periodic Reporting for period 3 - MYOCURE (Development of an innovative gene therapy platform to cure rare hereditary muscle disorders)
Reporting period: 2019-01-01 to 2019-12-31
MYOCURE seeks to overcome the bottlenecks that hamper muscle-directed gene therapy by:
-Boosting gene transfer and expression.
-Minimizing undesirable immune reactions and improving the efficacy and safety.
-Developing a scalable GMP-like manufacturing process.
-Applying for an orphan drug designation for the innovative advanced therapy medicinal product (ATMP) to ultimately justify a Phase I gene therapy clinical Trial
The main impact of MYOCURE is to advance the development of new therapies for patients with rare muscle diseases. MYOCURE will impact directly on an estimated 20,000 people in the EU suffering from MTM or GSD II. MYOCURE aims to exert a direct positive impact on the lives of MTM and GSD II patients by delivering novel treatment option(s) that will: (i) provide a long-term solution to life-threatening muscle disease and severe myopathy; (ii) exclude or significantly diminish the need for repeated sub-optimal medication by enzyme replacement therapy (ERT); (iii) be safer than the state-of the-art gene therapy options. MYOCURE will pave way towards the development of next-generation gene therapies aiming to improve the quality of life (QoL) of the afflicted patients (and their families). This will in turn impact on the health-care costs by aiming to achieve sustainable therapeutic solutions for the afflicted patients.
In addition, novel insights were obtained in some of the immune mechanisms after AAV gene therapy, defining a possible role for monocyte-derived dendritic cells and natural killer cells in AAV capsid immunity. Synthetic tolerogenic nanoparticles encapsulating rapamycin, co-administered with AAV vectors, prevented the induction of anti-AAV capsid humoral and cell-mediated responses. This allowed for successful vector re-administration in mice and nonhuman primates. AAV gene transfer with tandem promoter design (i.e. muscle and liver) prevented anti-transgene immunity and provided persistent efficacy in neonate Pompe mice. Secretable GAA showed improved therapeutic efficacy and lower immunogenicity compared to nonengineered GAA. These advances opens potential new avenues for the modulation of vector and/or transgene immunogenicity.
Hence, MYOCURE has significantly advanced the development of new therapies for patients with rare muscle diseases which will ultimately directly impact on the patients and their families and with implications beyond MTM and GSD II. MYOCURE has enhanced EU’s expertise and develop innovations meeting the needs of European and global markets in the field of orphan and rare diseases and has fostered the improvement of medical knowledge and competitiveness of Europe in the field of gene therapy technologies which will further strengthen its indirect economic impact.