Professor Stephen Wilton
Head, Molecular Genetic Therapies Group; Executive Director of Translational Rsearch and Development
Steve Wilton completed his PhD in the Biochemistry Department, University of Adelaide before PCR technology became available. He was appointed Chief Production Biochemist for a small biotechnology company in the University of Adelaide before being lured to another biotechnology company in Western Australia in 1987. Research was far more challenging than production biotechnology and he joined the Australian Neuromuscular Research Institute in 1991, working with Professor Nigel Laing to develop and apply molecular diagnostic tests for genes implicated in various neuromuscular conditions.
During diagnostic screening development for Duchenne muscular dystrophy (DMD), shorter than expected gene transcripts were observed and these were identified as having arisen from natural, but sporadic and low level exon skipping. This prompted further studies into this phenomenon, which was assumed to give rise to the rare dystrophin-positive "revertant fibres" detected immuno-histochemically in dystrophic muscle. Increasing the frequency of these revertant fibres may offer a new therapeutic avenue to treat this relentlessly progressive childhood muscle wasting disorder.
He is now the Head of the Molecular Genetic Therapy Group and the Molecular Genetic Research Services located at the ANRI. The MGTG group is pursuing a variety of antisense oligomer based approaches to modulate gene expression, primarily through re-directing the splicing process. Antisense oligomers were first shown to suppress abnormal splicing in a defective globin gene, and this approach was applied to normal splice motifs to excise targeted dystrophin exons, first in cells from animal models of dystrophin mutations, and then the human gene transcript. In just over a decade, the concept of dystrophin exon skipping has progressed from in vitro studies in myogenic cell cultures to human clinical trials.
MGTG research has focussed on developing exon skipping as a therapy for all amenable DMD mutations, where over 800 antisense oligomers have been designed and tested against this one gene transcript. This experience with antisense oligomer based splice switching has allowed the technology to be applied to other conditions, including Spinal muscular atrophy, asthma, Alzheimer's Dementia, Myotonic Dystrophy and Parkinson's Disease.
Steve is a member of the MDEX consortium, which has now published results of its successful Phase I clinical trials in the UK to evaluate exon skipping as a therapy for Duchenne muscular dystrophy. Phase II will be commencing in a multidisciplairy trial undertaken by an ANRI clinical team. With dystrophin being successfuly produced by boys in the higher dose range tn the UK trial these local trials are greatly anticipated.