An international team lead by UK researchers at the Centre for Neurodegenerative Research (CNR) at Kings College, London, have discovered a genetic variation that prolongs survival in people affected with motor neuron disease (MND). In a study of over 5,000 people in six countries - almost half of whom were affected with the disease - people with two copies of the so-called 'hero' variant of the KIFAP3 gene survived more than a year longer, on average, than others. The variant, reported in the journal Proceedings of the National Academy of Sciences, is the first of its kind to be discovered; working out how it prolongs life could now lead to new gene therapies and drug development for the treatment of MND.
MND destroys the motor nerve (or neuron) cells which make connections between the brain and muscles, progressing rapidly so that affected people are eventually unable to walk, talk or feed themselves. Cognitive abilities; intellect, memory and the senses are usually unaffected. The vast majority of those affected die from the disease within 2-5 years, half die within 14 months of diagnosis and five a day die in Britain alone. Yet the cause of the disease is still unknown. Only one drug to date, Riluzole, can extend life expectancy, by a few months, which means that care for the 5,000 British people currently affected by MND is mostly palliative.
The current study was prompted by the small minority of affected people who appear to be more resistant to the disease progression. Over 300,000 genetic variants were analysed using DNA from 2,359 people with MND and 2,814 people who were unaffected. People with two copies of a particular variant of the KIFAP3 (kinesin-associated protein 3) gene, which is involved in transporting essential molecules throughout nerve cells, survived on average a year and four months longer than others with MND.
Dr Brian Dickie of the Motor Neurone Disease Association (MNDA), hailed the discovery as 'a significant finding, bearing in mind the speed with which motor neurone disease can progress in patients'.
The challenge now, as highlighted by Professor Robert Brown, of the University of Massachusetts, 'is to turn this new knowledge into effective treatments'. It is hoped that more information on how this version of the gene slows progression of the disease will lead to new drugs designed to combat MND, although these are unlikely to appear within the next ten years. In addition, understanding variation in the gene itself will help to develop gene therapies that directly exploit the effect of this variation, according to the lead researcher in the study, Professor Ammar Al-Chalabi.