A third treatment developed by a Western Australian research team to treat Duchenne muscular dystrophy has received accelerated approval by the United States Food and Drug Administration (FDA).

American biopharmaceutical company, Sarepta Therapeutics (Cambridge, MA), has announced that the drug casimersen is now available in the US. The drug has the potential to treat eight per cent of patients with Duchenne by skipping exon 45 during dystrophin expression.

Casimersen (Amondys 45) and the two other gene-patching drugs approved by the FDA for Duchenne were developed through the pioneering research of Professors Sue Fletcher and Steve Wilton at the Perron Institute, and licensed through The University of Western Australia. Each drug is designed to treat a specific type of dystrophin gene mutation and this required testing in separate clinical trials.

Sarepta Therapeutics is focused on the development of precision genetic medicines and gene therapies to treat rare neuromuscular and central nervous system diseases.

Duchenne muscular dystrophy, occurring mainly in boys, is the most common childhood form of muscle wasting and is caused by a genetic error that prevents the body from producing dystrophin, a protein essential for maintaining muscle fibre strength and stability.

In the absence of dystrophin, muscle is much more susceptible to damage during regular activity, leading to loss of muscle and ultimately the ability to walk and breathe. Most children with Duchenne require a wheelchair before their early teens.

Billy Ellsworth, receiving treatment with the first Duchenne drug, eteplirsen (Exondys 51) developed by Professors Wilton and Fletcher and their team, is over 20 years of age and still able to walk. This initial exon 51 skipping drug targets approximately 10-13 per cent of Duchenne patients.

In 2019 a second drug, golodirsen (Vyondys 53) received US FDA accelerated approval to treat approximately 8-10 per cent of patients with a confirmed dystrophin gene mutation amenable to exon 53 skipping.

The three drugs for Duchenne developed by Professors Fletcher and Wilton, licensed to Sarepta and now available in the US, can treat almost 30 per cent of patients diagnosed with Duchenne.

The Molecular Therapy lab is now based at the Centre for Molecular Medicine and Innovative Therapeutics at Murdoch University, a joint research centre with the Perron Institute.

“This is a special day for Duchenne patients and offers great hope for patients living with rare diseases,” Professor Sue Fletcher said.

“There are more than 7,000 rare diseases that, when combined, affect about 6-8 per cent of the global population.”

“Our platform technology developed for Duchenne muscular dystrophy is currently being applied to other diseases. We are exploring the application of this approach to many serious conditions, such as asthma, motor neurone disease, multiple sclerosis and possibly even COVID-19 infections,” Professor Steve Wilton said.

Channel 7 Perth’s Flashpoint program featured the pioneering drug discoveries and the complexities of accessing them here in Australia on Monday evening (29 March). On the panel: Mike Atkinson (local father of two boys with Duchenne), Hayley Lethlean (Muscular Dystrophy WA CEO) and Prof Steve Wilton (Perron Institute and CMMIT, Murdoch University Director). Tim McMillan was the host.

Additional information

In the 1960s, Perron Institute Founding Director Emeritus Professor Byron Kakulas discovered that degenerated muscle tissue in Rottnest Island quokkas could regenerate when this small Australian marsupial was administered vitamin E.

This discovery was a momentous observation. Although ultimately not directly relevant to Duchenne muscular dystrophy, it showed that muscle wasting could be reversed. This breakthrough stimulated and revolutionised world research in the field, leading ultimately to the treatments developed at the Perron Institute by Professors Steve Wilton and Sue Fletcher for sufferers of Duchenne muscular dystrophy. The Molecular Therapy lab is now based at Murdoch University.

In totality, their work leading to the approval of three drugs is a rare achievement – something most scientists strive for but do not often accomplish in their entire careers.

The development of the drugs was made possible by significant and long-term support from the Perron family, Telethon, Muscular Dystrophy WA, Muscular Dystrophy USA, the US National Institutes of Health and the Australian National Health and Medical Research Council.

Other treatments currently in various experimental phases at the Centre for Molecular Medicine and Innovative Therapeutics (Perron Institute-Murdoch University) are for rare diseases such as adult onset Pompe’s disease, spinal muscular atrophy, inherited retinal diseases, Charcot-Marie-Tooth 1A.

Professor Steve Wilton is the Director of both the Perron Institute in Nedlands and the Centre for Molecular Medicine and Innovative Therapeutics (CMMIT) at Murdoch University.

Professor Sue Fletcher is based at CMMIT and PYC Therapeutics in Nedlands where she is the Chief of Research and Development.