Genome Editing for Neuromuscular Diseases

Neuromuscular diseases are a diverse range of conditions that include myopathic and neuropathic disorders related to muscular dysfunction. Inherited neuromuscular diseases are the result of a broad spectrum of genetic mutations, including point mutations, insertions and deletions, chromosomal rearrangements, epigenetic aberrations, and repeat expansions or contractions. Targeted genome editing is a promising method to correct the inherited mutations underlying these disorders. Over the last decade there have been many significant advances in engineering targeted DNA-binding proteins to manipulate specific sequences of complex genomes. These genome editing tools are rapidly becoming viable therapeutics that will allow the targeted addition, exchange, or removal of almost any genetic sequence in the human genome. In this chapter, selected neuromuscular diseases representing inherited myopathies or neuropathies are discussed. The genome editing tools available to create targeted genetic modifications are reviewed. Promising cell-and gene-based therapies are introduced in the context of the treatment of neuromuscular disorders in combination with genome editing therapies. Finally, specific examples of how genome editing may be applied to correct the genetic basis of particular neuromuscular disorders are presented and discussed.