Motor neurone disease: Edinburgh scientists reveal breakthrough

By Rosie Mcfadyen

A group of scientists led by Dr. Arpan Mehta in the Euan MacDonald centre have published a breakthrough paper for Motor Neurone Disease research. Motor Neurone Disease (MND) also known as Amyotrophic Lateral Sclerosis (ALS) is characterised as the loss of upper and lower motor neurons that are involved in voluntary muscle contraction. Sclerosis of motor neurons usually starts in the neuromuscular junctions (NMJ) which is the point of transmission of electric potential between the axon and the muscle. The selectivity of neuronal degeneration is still under active research, but is thought to be related to an interruption of the glutamate-mediated communication between neurons (Van den Bosch, 2006). Most current MND drugs approved by the FDA target glutamate regulation, as well as pain regulation drugs and treatment for respiratory failure associated with NMD. The recent research, published by Mehta et al. 2021 shows a new identifiable characteristic of MND neurons that is a possible target for treatment. The main medication used for treatment called Riluzole only increases survival of patients by around 2-3 months, this is why the findings are crucial as they may offer a more effective treatment solution. Mehta et al. used analysis of patient derived pluripotent stem cells as well as patient post mortem tissue analysis to identify key differences in axonal length and mitochondrial movement within the axons between control and affected cells. 

The study used cells derived from MND patients as well as healthy subject-derived transgenic cells, using the C9orf72 gene which is known to cause about half of all familial MND cases. Around 80% of MND cases are ‘sporadic’ meaning they are not familial or related to any known genes (Mehta et al. 2021). The pathophysiology for underlying MND is currently indistinguishable from familial, meaning that using the familial version for the study will likely apply to the sporadic type. It was established in the study that C9orf72 motor neurons have “dysfunctional axonal homeostasis” as well as abnormalities in axon morphology, specifically length and transport of cargo. These irregularities were thought to be attributed to impaired mitochondrial respiration via mitochondrial RNA sequencing where a deficit in electron transport chain transcripts were observed in the motor neuronal mitochondria of C9orf72 cells. 

The identification of this new target for drug therapy is a huge breakthrough for MND patients. Following the publication of their paper, the team are undergoing further experiments to identify existing FDA-approved drugs for mitochondrial regeneration that can be used to treat MND patients. The restoration of mitochondrial number and function will hopefully restore axon length, cargo transport and potentially reverse axonal damage associated with MND. 

Sources

“Amyotrophic Lateral Sclerosis (ALS) Fact Sheet”, NINDS, Publication date June 2013. NIH Publication No. 16-916

Mehta, A.R., Gregory, J.M., Dando, O. et al. Mitochondrial bioenergetic deficits in C9orf72 amyotrophic lateral sclerosis motor neurons cause dysfunctional axonal homeostasis. Acta Neuropathol 141, 257–279 (2021). https://doi.org/10.1007/s00401-020-02252-5 

Van den Bosch L. [The causes and mechanism of selective motor neuron death in amyotrophic lateral sclerosis]. Verh K Acad Geneeskd Belg. 2006;68(4):249-69. Dutch. PMID: 17214440.

One thought on “Motor neurone disease: Edinburgh scientists reveal breakthrough

  1. Huge breakthrough? Well I would be careful with such claims. I wish these scientists every success, no doubt. However they are on wrong path – this will not work. If I am wrong and it will, I will send an honest apology. The problem of MND is somewhere else and it is being ignored to great extent (infections, mercury et al. intoxciation). So lets see what the truth is.

    https://alsexperimentaltheory.com/2021/04/25/als-1kd-challenge-interview/

    Like

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