Genetic approaches for the diagnosis and treatment of inherited muscle diseases have advanced rapidly in recent years. Many of the advances have occurred in the treatment of Duchenne Muscular Dystrophy (DMD), a muscle wasting disease where affected boys are typically wheelchair bound by age 12 years and generally die from respiratory failure or cardiomyopathy in their twenties. DMD is caused by mutations in the dystrophin gene encoding the large cytoskeletal protein which associates with other proteins at the muscle membrane to form the dystrophin-associated protein complex (DAPC). In the absence of dystrophin, the DAPC is lost, making the muscle membrane more susceptible to contraction-induced injury. The identification of the gene causing DMD in 1986 resulted in improved diagnosis of the disease and the identification of hotspots for mutation. However there is currently no effective treatment.
There are several promising genetic therapeutic approaches at the preclinical stage or in clinical trials including exon-skipping, read-through of stop codons, delivery of dystrophin minigenes and the modulation of expression of the dystrophin related protein, utrophin. This lecture will provide a summary of the current status of DMD therapy with a particular focus on the modulation of utrophin expression, an approach that is applicable to all DMD patients whatever their mutation.
Professor Dame Kay Davies, Ph.D., DBE FMedSci FRS is the Professor of Genetics Emeritus and co-Director of the MDUK Oxford Neuromuscular Centre in the Department of Physiology, Anatomy and Genetics at the University of Oxford. She received a BA degree in Chemistry and a graduate PhD degree in Biochemistry from the University of Oxford. She was appointed Professor of Genetics in 1996 and then appointed Dr Lee’s Professor of Anatomy at the University of Oxford in 1998. She established and was Director of the MRC Functional Genomics Unit 1999-2017 and co-founded the Oxford Centre of Gene Function in 2000 with Professors Ashcroft and Donnelly, a new institute going from genetic association in human disease to function in the whole organism. Kay’s research interests lie in the molecular analysis and development of treatments for human genetic diseases, particularly Duchenne muscular dystrophy (DMD), and the application of genomics for the analysis of neurological disorders. She has published more than 400 papers and won numerous awards for her work and co-founded companies to translate her work to the clinic. Kay is a founding Fellow of the Academy of Medical Sciences and a Fellow of the Royal Society. She was appointed Governor of the Wellcome Trust in 2008 and became Deputy Chair 2013-17. She chairs the Genome England Clinical Interpretation Partnership in the UK and is a member of the GRL Board at the Sanger Institute. She is very committed to the public understanding of science and the ethical issues raised by human genetics research. She co-chaired with Dr Rick Lifton, the International Commission on the Clinical Use of Human Germline Genome Editing which produced a report in 2020. She has done numerous television and radio interviews including Desert Island Discs. In 1992, she founded and edited the successful genetics journal Human Molecular Genetics before stepping down this year. She was made Dame Commander of the British Empire for services to science in 2008.