MND study provides new focus for potential drug treatments.

Motor neuron disease treatments that boost energy in nerve cells could be developed thanks to new research.

Dr Arpan Mehta alongside Dr Bhuvaneish Selvaraj and Professor Siddharthan Chandran from the Euan MacDonald Centre for MND Research have published a laboratory study that sheds light on how the damage to nerve cells caused by motor neuron disease (MND) can be repaired by improving the energy levels in mitochondria – the power supply to the motor neurons.  Researchers have discovered that, in human stem cell models of MND, the axon, the long part of the motor neuron cell that connects to the muscle, is shorter than in healthy cells. Also the movement of the mitochondria, which travel up and down the axons, is impaired. The scientists showed that this was caused by a defective energy supply from the mitochondria and that by boosting the mitochondria, the axon reverted back to normal.

The researchers used stem cells taken from people with the C9orf72 gene mutation that causes both MND and frontotemporal dementia. They used these stem cells to generate motor neuron cells in the lab to use in their experiments.  The study also examined human post-mortem spinal cord tissue from people with MND who had kindly donated their tissue through the Medical Research Council Edinburgh Brain and Tissue Bank. The results supported the findings from the stem cells.

MND, also known as amyotrophic lateral sclerosis or ALS, is a progressive condition that causes muscles to waste away. It occurs when nerve cells called motor neurons, which send messages from the brain and spinal cord to the body’s muscles, stop working properly. More than 1500 people are diagnosed with MND in the UK each year. There is no cure and half of people affected die within two years of diagnosis.

Although the research focused on the people with the commonest genetic cause of ALS, researchers are hopeful that the results will also apply to other forms of the disease. The results of the study are now being used to look for existing drugs that boost mitochondrial function and may be able to be repurposed to treat MND.

Dr Arpan Mehta, Lady Edith Wolfson Fellow and PhD student at the University of Edinburgh, said: “The importance of the axon in motor nerve cells cannot be overstated. Our data provides hope that by restoring the cell’s energy source we can protect the axons and their connection to muscle from degeneration. Work is already underway to identify existing licensed drugs that can boost the mitochondria and repair the motor neurons. This will then pave the way to test them in clinical trials.”

The study was funded by the Medical Research Council, Motor Neurone Disease Association, Euan MacDonald Centre for MND Research, My Name’5 Doddie Foundation, UK Dementia Research Institute and Anne Rowling Regenerative Neurology Clinic.

There are some lovely time-lapse films on the University Mediahopper channel, showing mitochondria travelling along an axon in a motor neuron (nerve cell): Film 1a – from a healthy motor neuron Film 1b - from a damaged motor neuron with the C9orf72 gene Film 2a - from a damaged motor neuron with the C9orf72 gene after boosting the mitochondria

Photograph: Bhuvaneish (rear) and Arpan (front right), with Euan MacDonald, who lives with MND.