Research grants on facioscapulohumeral dystrophy prove useful as genetic basis is found

By Dr. Ananya Mandal, MDMay 8 2012

Businessman Bill Moss’s determination to fight his untreatable muscle-wasting disease may have paid off. Four years ago, Mr Moss, a former Macquarie Bank Executive Director, established a charitable research foundation, FSHD Global, which partly funded the Italian researchers who made the breakthrough.

Until then, there had been no government money in Australia, and very little overseas, for studying the poorly diagnosed disease, which may affect as many as one in 7,500 people and which leads to a weakening of the muscles in the face, shoulders, and limbs. The foundation has supported 17 research projects in Australia and around the world.

Symptoms of Facioscapulohumeral Dystrophy (FSHD) usually develop during the teen years, with most people noticing some weakness by the age of 20 years. The disease generally progresses slowly, but it can cause significant functional impairment and can interfere with the ability to adequately convey emotions through facial expressions. Facioscapulohumeral Dystrophy is inherited in an autosomal dominant pattern, meaning it is only necessary to inherit and show symptoms of the disease-causing mutation from one parent.    

Now researchers have found that a defect in gene regulation - one never seen before in a human disease - leads to this common form of muscular dystrophy known as FSHD. The discovery not only gives hope to people with the hereditary crippling condition but it may also have an impact on research on other genetic diseases, such as cancer and diabetes.

Scientists had known since 1992 that the disease was linked to a reduced number of specific, repeated units of DNA on chromosome 4. It was assumed this defect switched off genes, preventing protein production. Researchers led by Davide Gabellini, however, showed the opposite was true: sufferers had an excess of protein production.

Dr Gabellini, of the San Raffaele Scientific Institute in Milan, and his colleagues have now determined the unusual mechanism responsible for this effect. Their results are published in the journal Cell.

The researchers note that loss of the repeated units leads to production of a specific piece of RNA genetic material that allows genes to become hyperactive. Blocking production of the RNA led to normal gene function, making it a target for drug development. Dr Gabellini said repeated units of DNA are found near genes linked to other diseases, such as diabetes. “There is a good chance that alterations in other repetitive sequences in our genome are responsible for bad gene regulation in other diseases.”

The Muscular Dystrophy Association (MDA) in its announcement expressed happiness. “This is an exciting new development in FSHD,” said MDA Vice President of Research Sanjay Bidichandani. “We're possibly a step closer in the development of a therapy for FSHD, and we at MDA are pleased to have been able to provide significant support to the investigators who are making this happen.” “These findings from Dr. Gabellini's group demonstrate the power of MDA's development grant program,” Bidichandani said. “We identify promising young investigators and nurture their development into leading neuromuscular disease researchers.”