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Page 29
Cell and Gene Therapy 2018 & Clinical Microbiology Congress 2018
Biomedical Research
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ISSN: 0976-1683
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Volume 29
S e p t e m b e r 1 0 - 1 1 , 2 0 1 8 | D u b l i n , I r e l a n d
allied
academies
Joint Event on
CLINICAL AND MEDICAL MICROBIOLOGY
CELL AND GENE THERAPY
&
World Congress on
International Conference on
Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C3-008
OVERCOMING ADENO-ASSOCIATED VIRUS GENE THERAPY LIMITATIONS
IN GENETIC NEUROMUSCULAR DISEASES
Giuseppe Ronzitti
Université Paris-Saclay, France
N
euromuscular diseases represents a major hurdle for patients, families and the society in its entirety. Rare, genetic
neuromuscular diseases constitute a bigger challenge given the absence of knowledge on the physiopatological mechanisms
and of therapeutic options. In the last years, adeno associated virus (AAV) vector-based gene therapy became a principal actor
in the development of therapies for monogenic diseases. Successful human trials of gene transfer in the liver for hemophilia A
and B, in the eye for congenital blindness and in the nervous system for spinal muscular atrophy have unveiled the therapeutic
potential of this viral vector platform. However, one of the main limitation of AAV gene therapy is the high dose of vector needed to
rescue neuromuscular diseases. Doses used in the clinic for these disorders are hardly produced and are likely to induce unwanted
secondary effects. Another constraint in the use of AAV vector is their limited size of transgene encapsidation. This is of particular
relevance in genetic neuromuscular diseases that frequently involve large transgenes. Here, using glycogen storage disorders
as model diseases, we developed some technological tools to overcome the current limitations of AAV gene therapy applied to
neuromuscular diseases.