Steve Wilton is one of the pioneers in the development of personalised alternative splicing therapies to treat Duchenne muscular dystrophy (DMD), the most common and serious form of childhood muscle wasting. He first showed that antisense oligonucleotides could redirect dystrophin pre-mRNA processing in a mouse model of DMD by skipping the mutated exon and restoring functional dystrophin expression. He has been at the forefront of dystrophin exon skipping for many years, developing many splice switching oligonucleotides and strategies for DMD and other conditions. He identified the in vitro limitation of the morpholino oligomers as delivery, and proposed that these compounds are clinically relevant for exon skipping. His group designed the first morpholino oligomer targeting dystrophin exon 51 (eteplirsen), which is now in extended Phase 2b clinical trials in the USA, sponsored by Sarepta Therapeutics. After two years, DMD trial participants receiving weekly doses of eteplirsen have maintained the same levels of ambulation as when the trial first began. This stabilisation of the muscle wasting is unprecedented.
Eteplirsen is licenced through the University of Western Australia, and his group continues to work on refining new DMD compounds with Sarepta Therapeutics. This work has been recognised with the 2012 Western Australian Innovator of the Year award, and more recently, the 2013 Australian Museum Eureka Award for Translational Medicine. Although results from Sarepta’s eteplirsen trials are most encouraging, there is still a daunting amount of work ahead. In particular, clinical trial design with limited patient numbers, addressing all possible DMD mutations and gaining regulatory approval to bring multiple different drugs to the clinic to treat one rare disease.
Steve completed his PhD under the guidance of Professor George Rogers (AO PhD DSc FAA) in the Department of Biochemistry, University of Adelaide, and began working with Professor Nigel Laing in the Australian Neuromuscular Research Institute (ANRI) in 1991. While developing diagnostic tests for neuromuscular diseases, he started working with Professor Sue Fletcher on various therapeutic strategies, including gene replacement, gene editing, nonsense mutation read-through and exon skipping. They are now applying therapeutic alternative splicing to other genetic disorders, including spinal muscular atrophy, multiple sclerosis and cystic fibrosis.Steve was appointed Director of the Western Australian Neurosciences Research Institute (previously ANRI) in February 2013, and took up the Foundation Chair in Molecular Therapies in the Centre for Comparative Genomics, Murdoch University, in March 2013. He remains head of WANRI’s Molecular Genetic Therapy Group, and tries to remain sane by cooking, drinking wine, fishing and scuba diving (now with a shark shield!).