Discovery of gene abnormality that causes the fatal paralysis, motor neuron disease

In a world first, University of Sydney researchers from the ANZAC Research Institute at Concord Hospital, in collaboration with colleagues at Kings College London, have found a new gene abnormality that causes the fatal paralysis, motor neuron disease (MND).

This was identified in affected members of some MND families as well as some isolated MND cases. "Although the abnormal gene is only present in a small number of cases, the exciting aspect of this discovery is that it codes for a protein that is actually abnormal in all MND cases" says Ian Blair, the lead Australian author in the study.

Ninety per cent of MND cases are sporadic, while the remainder occur in families as an inherited disease. This newly identified abnormality causes both familial and sporadic forms of MND.

Garth Nicholson, a senior author in the study says, "This is an exciting finding that will initiate a new chapter in MND research. Up to now it was not known whether this gene was assisting brain repair or causing the death of nerve cells".

The gene, called TDP-43, has previously been shown to form abnormal protein aggregates in nerve cells of MND. "The discovery of families and sporadic cases with faulty versions of this gene now proves its involvement in the disease".

MND causes the death of motor nerves (neurons) that extend from the brain and spinal cord to all the muscles in the body, controlling the ability to move, breathe, eat, and drink. People with MND, which onsets later in life, are gradually confined to a wheel chair, and breathing difficulties can follow. The disease can progress rapidly, with death typically 3 to 5 years after onset although there are long living exceptions.

Work has now commenced to understand how the abnormal gene causes MND. "This offers a rare window of opportunity to find how this protein becomes toxic and causes motor neuron loss" says Blair. "This will have crucial implications for understanding MND as a whole".

There are no effective treatments for MND. "This is an important step in a long term effort to identify better diagnostic tools and effective treatments" stresses Nicholson.

The study, published in the journal Science, is a culmination of over 10 years of research assisted by the dedicated cooperation of families with inherited MND, through the ANZAC Research Institute.