Novel discovery in motor neuron disease may pave the way for future treatments

Written by Frances Adlam, Future Science Group

Researchers from the University of Sheffield (UK) have discovered a potential approach to reduce the death of nerve cells, therefore preventing the progression of many neurological diseases. The results from the study, recently published in Nature Neuroscience, present a novel way to treat the most common type of motor neuron disease (MND), Amylorophic Lateral Sclerosis (ALS).
ALS is caused by a mutation in the C9ORF72 gene and accounts for 40-50% of inherited MND cases and 10% of all MND cases. There are currently no treatments available for patients suffering from ALS leading to a life expectancy of 3–5 years.

In an earlier study researchers examined neurons and found an accumulation of R-loops and increased DNA breakage in the C9ORF72 gene can lead to neurodegenerative diseases. Despite the repair tool kits in our cells, many die due to the overexpression of autophagy.

In the present study, jointly led by Sherif El-Khamisy and Mimoun Azzouz (both University of Sheffield), researchers utilized genetic techniques in cellular and murine models of MND and were able to shut down the over expressed degradation process.

“Even though the DNA was still damaged, the cells were able to cope and did not die. Discovering this new mechanism and its consequence is a significant step towards developing new therapies for motor neurone disease and other neurodegenerative conditions,’ explained El-Khamisy.

There are hopes that these novel findings may also explain the death of nerve cells in diseases such as Alzheimer and Parkinkson’s, as well as the ageing process. However further work needs to be conducted to confirm these findings.

“The research paves the way for an exciting horizon to accelerate the pace of therapeutic development for MND. Our aim now is to identify targets that can preserve the DNA tool kits and rescue neurons from degeneration,” concluded Azzouz.

Source: Walker C, Herranz-Martin S, Karyka E et al. C9orf72 expansion disrupts ATM-mediated chromosomal break repair Nature Neuroscience doi:10.1038/nn.4604 (2017);  The University of Sheffield press release