Researchers illuminate cause of crippling genetic disease

Scientists at the University of Edinburgh are closer to correcting an abnormal gene which causes one of the crippling muscle wasting diseases known collectively as Charcot-Marie-Tooth (CMT) disease. Their findings may lead to the development of gene therapy to treat patients with CMT disease, it is reported in the current issue of Nature (9 September).

CMT affects around 23,000 people in the UK. It leads to muscle weakness and wasting in the feet, lower legs, hands and forearms and can confine those with the condition to a wheelchair. The researchers describe the role of the gene Periaxin in causing CMT.

University of Edinburgh researchers, working with colleagues in Paris, first identified Periaxin as one of the genes implicated in CMT disease in 2001.The new research, funded by the Wellcome Trust, has shown that the protein produced from this gene has a vital role in allowing the insulation around the nerves to stretch as nerves get longer during body growth. If the Periaxin gene is faulty, the insulation, known as myelin, stays as short segments and the nerves cannot conduct impulses quickly. This, in turn, means that patients lose the ability to walk.

Professor Peter Brophy, Director of the Centre for Neuroscience Research at Edinburgh University, and lead author of the paper, said: “Researchers have now identified about half of the 30 or so different genes which are responsible for inherited disease affecting the peripheral nervous system, but developing treatments has been difficult since, for most of these genes, we don’t understand their normal function. The Periaxin gene is one of the few for which we now understand its role in nervous system function. The next step is to try to develop gene therapies to correct the abnormal gene carried by patients with this highly disabling disease.”

He added: “The major reason for studying genetic diseases in the human population is to try to develop treatments for the diseases. However, an important spin off is that these diseases can provide new understanding into human biology and the work on the Periaxin gene is a good example of this. As well as providing important insight into why patients with CMT disease become disabled, for the first time we now have a clear view of the importance of the length of the insulated segments around nerves, in determining how nerves work.”