Major review contributes to knowledge of motor neuron disease

Date 4 May 2021

Dr Björn Vahsen identifies the need to take account of non-neuronal cells in future drug development

Dr Björn F Vahsen, DPhil candidate in Clinical Neurosciences, has published a major review on ‘Non-neuronal cells in amyotrophic lateral sclerosis – pathogenesis to biomarkers’ in Nature Reviews Neurology.

Björn VahsenAmyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal neurological disorder with a lifetime risk of ~1:400 that results in progressive paralysis due to the degeneration and death of motor neurons in the brain and spinal cord. People with ALS usually die within three years from symptom onset, with only two licensed drugs with very moderate effects on survival and disease progression currently available. Research into ALS has classically been highly focused on the dysfunction of nerve cells, but there is now increasing appreciation of the contribution of non-neuronal cells to the disease.

The review article summarises and analyses the evidence for the involvement of these non-neuronal cells (microglia, astrocytes, oligodendrocytes and peripheral immune cells) in ALS, evaluating studies on human tissue as well as cellular and animal models. The review concludes that most evidence agrees on a toxic role for non-neuronal cells in ALS, which actively contribute to motor neuron degeneration, and that it will be important to take non-neuronal cells into account in future mechanistic studies and drug development. 

Professor Zoltán Molnár commented:

‘I am delighted to see that a St John’s DPhil student has made such a considerable contribution to identifying disease-modifying therapy for this devastating neurodegenerative condition.  Björn’s review will change the motor neuron-centric view of amyotrophic lateral sclerosis (ALS) pathogenesis and will draw attention to the crucial role of non-neuronal cells in homeostatic functions within the CNS.  The review shifts the paradigm to study the interactions with microglia and astrocytes, in crosstalk with peripheral immune cells in relation to the pathogenesis of ALS.’

Dr Vahsen is based at the Oxford Motor Neuron Disease Centre in the Nuffield Department of Clinical Neurosciences.