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A jump in the share price of a pharmaceutical company has signalled significant success for medical researchers at UWA, in their quest to treat Duchenne Muscular Dystrophy (DMD).

A 150 per cent jump in the trading price of Sarepta Therapeutics shares last month came after clinical trials at the Nationwide Children's Hospital in Ohio US offered the first evidence that the antisense drug Eteplirsen had a significant positive effect on DMD patients.

Professors Sue Fletcher and Steve Wilton, from the Australian Neuromuscular Research Institute (ANRI ) and UWA 's Centre for Neuromuscular and Neurological Disorders, have been working for years on the idea of enabling the production of the protein dystrophin, which is missing in patients with DMD .

Clinical trials on a compound developed in their laboratory, which has been licensed by UWA to Sarepta for development, have been run in the UK in 2009-10, and the US over the previous nine months, the research supported mainly by two US National Institutes of Health grants.

This latest trial involved treating patients with an exon-skipping compound once a week over 36 weeks. The boys were assessed by the ‘six minute walk test' and those who received the treatment were able to walk 69.4 metres further than the boys who were on a placebo.

"The magnitude of this clinical benefit is an unprecedented treatment effect in DMD ," said Dr Jerry Mendell, Director of the Centers for Gene Therapy and Muscular Dystrophy at Nationwide Children's Hospital.

"This result represents a major advance in the pursuit of a diseasemodifying treatment for this severe, progressive and life-threatening disease. The six-minute walk test results with Eteplirsen, combined with its safety profile to date, make Eteplirsen the most promising advance to treat the underlying cause of muscular dystrophy I've seen in my more than 30 years in the field."

DMD is a rare, degenerative neuromuscular disorder causing severe, progressive muscle loss and a premature death. DMD affects approximately one in every 3,500 boys worldwide. It is associated with specific inborn errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle.

At least three boys with DMD are born in Perth each year. They are usually in a wheelchair by the age of 12.

DMD affects all muscles, including the heart. Eventually progressive muscle weakness leads to heart failure.

Assisted ventilation, medications and good clinical care improve the health and extend the lives of DMD sufferers, but the condition is terminal, and death usually occurs before the age of 30.

Professor Fletcher explained that exons are the protein coding components of Steve Wilton and Sue Fletcher At least three boys with DMD are born in Perth each year genes. The large dystrophin gene has 79 exons and a complex expression pattern. "Many different dystrophin gene lesions can cause DMD, but the most common mutations flank exon 51 and disrupt the gene message. Our therapy works by tricking the cell machinery into skipping that exon and linking the remaining exons in such a way that the integrity of the gene message is restored and the code for the protein ‘makes sense', much like arranging words to link together to make sense of a sentence. The objective of the therapy is to restore some functional dystrophin production and slow down or stabilise muscle deterioration in DMD, giving the boys and young men a better quality of life. The difficulty in developing therapies of this nature is that different mutations require the design and development of different antisense compounds.

"Although a relatively small number of these drugs could help more than 70 per cent of DMD cases, many different antisense compounds will be required for all the other boys who have less common mutations."

The research group is collaborating with a clinic at the ANRI in the QE II Medical Centre, for young men in WA with DMD . "They are keen to take part and contribute to the research," Professor Fletcher said.

"The clinic staff and potential participants are waiting for test compounds to be made available. The process of drug development is costly, and Sarepta Therapeutics has already put over $100 million into the development of Eteplirsen."

The group has had difficulty winning adequate funding in Australia and has been supported mainly by US and European agencies, complemented by funds from special interest charitable groups in Victoria and WA .

Simon Handford, Associate Director of the Office of Industry and Innovation, the technology transfer office of UWA , explained that the licence with Sarepta had been crucial in terms of allowing for the technology to be given a chance of being translated from an idea in the lab to a treatment for patients.

"Drug development is notoriously challenging, with huge costs and complex regulatory approvals to overcome. Partnering is usually the only way that a university can access the funds and expertise required to conduct the necessary clinical trials and this recent result with Eteplirsen is a huge step forward to seeing a treatment developed at UWA being used to benefit patients."

Published in UWA News , 20 August 2012