Treatment hope for muscular dystrophy
An international team led by the University of Melbourne has found that increasing a specific protein in muscles could help treat Duchenne muscular dystrophy (DMD), a severe and progressive muscle wasting disease that affects young boys.
Approximately one in every 3,500 boys worldwide is affected by DMD. There is no cure for the disease which causes muscle fragility, spinal curvature and premature death.
Results from the studies published recently in Nature showed that by increasing levels of ‘heat shock protein 72’ (HSP72) in the muscles of animal models of DMD, muscle strength improved, the disease progression slowed and lifespan increased.
The research, led by Professor Gordon Lynch, Head of the Department of Physiology at the University of Melbourne and conducted by Dr Stefan Gehrig for his PhD, investigated several scientific approaches to increasing the levels of the protein.
The study was also performed in collaboration with Professor Mark Febbraio and his team at Baker IDI Heart and Diabetes Institute. Researchers from the University of Oxford and Deakin University also collaborated in the research.
One approach revealed that administering the drug BGP-15 (which increases HSP72) improved overall muscle function in limbs and the diaphragm, a muscle critical for breathing. In addition, the lifespan increased by 20 per cent.
The researchers also discovered that increasing HSP72 in muscles improved the function responsible for controlling calcium levels confirming it as a target for future therapeutic drugs for the disease.
“Our studies showed that by increasing HSP72, we can improve calcium pump function which could be a way to help reduce the muscle breakdown in boys suffering the condition,” Professor Lynch says.
“If these dramatic effects in mice can be repeated in patients, then the approach has the potential to delay loss of the ability to walk; delay when patients will need machines to help them breathe; and most importantly allow them to live longer, and with a better quality of life.
“We expect now that these exciting findings will serve as the basis for clinical trials in the near future,” he says.
Professor Mark Febbraio, who is also Joint Chief Scientific Director of N-Gene, the company which supplied BGP-15, said the drug was already in clinical trials for Type 2 Diabetes and hence, could potentially go into trials quite quickly within the next few years.
For Boris Struk, who has an adult son Ryan with muscular dystrophy, and who is Director of Muscular Dystrophy Australia, any research discovery, and particularly one that improves diaphragm muscle strength to assist breathing, is critical.
“What is so important for these young men affected by muscular dystrophy is to have the strength to breathe on their own,” he says.
“So this research is welcome news. Unfortunately the finding is too late for Ryan but it will help newly diagnosed boys.”
Now 32, Ryan has defied all the odds, as generally those affected by the condition do not live past their early twenties.
“When he was diagnosed we were told he would not survive beyond 14 or 15 years old,” Mr Struk says.
Even when he was a very little boy, his family knew there was something different about Ryan. Even the family pet would treat him differently.
“We had a robust German Shepherd who would jump all over our older boy Leon but would never jump on Ryan. He would stand next to him so Ryan could pat him. It’s like he knew he was different,” Mr Struk says.
Ryan was diagnosed at nearly four years old. He lost the ability to walk when he was nearly nine, when he went into a manual wheelchair and then into an electric one about a year later.
“This was a terrible time for us as parents realising how permanent his disability was, but Ryan was thrilled, because he said he could finally keep up with the kids at school.”
By age 14, because all his muscles were weakening, significant scoliosis, or curvature of the spine, had set in, making it very difficult for Ryan to breathe. It also caused constant tiredness, lethargy and problems in sustaining concentration.
Despite an operation to correct the curvature with steel rods from the hips to the base of the neck and thus improve his ability to breathe, Ryan got progressively weaker.
At the age of 18, Ryan had lost significant weight because it was difficult for him to eat without muscle strength. He had a peg tube inserted directly into his stomach to feed and became reliant on a ventilator 24 hours a day.
Ryan has, amazingly, been able to study short courses with only enough strength to lift his fingers to press a modified mouse.
“He has achieved so much and we are very proud of him,” Mr Struk says. “There’s no question this new research will help us on the path to accelerated treatment solutions.”