Neuromuscular Diseases

These devastating diseases are typically rare diseases and primarily affect children resulting in progressive muscle-wasting and life-span reduction.

Prof Wood has pioneered development of first and now second generation antisense oligonucleotide-peptide conjugate drugs (called PPMOs) that are designed to modulate RNA splicing by exon skipping or exon inclusion. These approaches have been shown to be highly effective at correcting the underlying molecular defects in animal models of DMD and SMA, respectively. In particular, PPMO technology is capable of targeting the heart muscle, which is a major advantage over other approaches as cardiac failure is one of the leading causes of death in DMD patients and is particularly important for DM1 therapy. In early 2018, Prof Wood founded a biotech spin-out company with colleagues Mike Gait and Caroline Godfrey, PepGen Ltd, which aims to advance PPMO drugs towards use in DMD and SMA patients.

While the genetic mutations that cause DMD and SMA have been known for many years, a detailed understanding of the molecular mechanisms that underlie these pathologies is currently lacking. The Wood lab has employed state-of-the art transcriptomic and proteomic technologies in order to better understand disease-associated gene expression changes. In particular, the Wood lab has investigated small RNA molecules called microRNAs which are involved in the regulation of gene expression in both normal biological processes, and in neuromuscular disease pathology. Specific microRNAs are elevated in the serum of DMD patients and animal models, are therefore promising minimally-invasive biomarkers for monitoring disease progression and response to therapy.