New mutation raises hope for advances in research
A newly identified cause of the rare inherited form of MND could open up a new avenue of investigation into the mechanisms underlying all forms of the disease, with the potential to dramatically advance research.
In a paper published in the prestigious journal “Science”, researchers led by Prof Chris Shaw at the Institute of Psychiatry, London, describe a family affected by the inherited form of MND in which those family members with the disease all have a mistake (mutation) in the genetic instructions for making a protein called TDP-43. Unaffected family members do not have the mutation, thus establishing that, in this particular family at least, the disease is directly caused by mutations in the TDP-43 gene.
Prof Shaw’s group went on to investigate the effects of the faulty TDP-43 protein produced by the mutated gene and, through a series of experiments in cultured cells and in chick embryos, have demonstrated that it can cause significant problems within the central nervous system.
Mutation is extremely rare
It is important to note that mutations in this gene are very rare and are the direct cause of only a very small number of cases of MND, even amongst those with the familial form of the disease. Prof Shaw’s discovery therefore does not open up the possibility of a new genetic test to identify people who might be at risk from the disease.
What does this discovery mean for someone affected by MND?
However, whilst mutations in the TDP-43 gene are only rarely a primary cause of the disease, it would seem that the TDP-43 protein itself somehow plays a role in most cases of MND. It has been known for some time that motor neurones affected by MND contain
abnormal clumps of protein molecules. In 2006 American scientists discovered that in the majority of cases of MND, TDP-43 is included in these clumps. However, until now scientists have only been able to speculate as to whether TDP-43 actually contributes to motor neurone degeneration or is an innocent by-product of the disease process. The findings of Prof Shaw’s group lend considerable weight to the theory that TDP-43 can be toxic to motor neurones and so contributes to the development of MND.
A springboard to greater understanding
Researchers now have the opportunity to delve deeper into this newly discovered disease mechanism, as well as develop new laboratory models of MND. Brian Dickie, Director of Research Development at the MND Association, said “The discovery of a new cause of the disease is of international importance. This new information will be a springboard to greater understanding of the processes that cause motor nerves to die - and it is through such understanding that we will develop the treatment strategies to defeat this devastating disease."
Research
