What Triggers Multiple Sclerosis? Scientists May Have Identified the Culprit

Scientists have identified a cellular mechanism that may be responsible for the development of multiple sclerosis (MS), and could serve as a target for future treatments.

There are an estimated 2.5 million individuals worldwide living with MS, and the cause remains unknown. However, scientists have long suspected that mitochondria may play a role in MS development.

In a study published in the Journal of Neuroinflammation, investigators combined clinical and laboratory experiments to show how mitochondria becomes defective in patients with MS.

Using human brain tissue samples, the results of the study showed that the protein Rab32 was largely present in the brain of patients with MS, but was virtually absent in healthy brain cells.

One of the hallmarks of neurodegenerative diseases is endoplasmic reticulum (ER) stress. In the new study, investigators found that ER stress is strongly associated with Rab32 upregulation in the progression of MS, which results in mitochondrial dysfunction and neuronal death.

“The induction of Rab32 and other MAM [mitochondria-associated membrane] proteins correlates with ER stress proteins in MS brain … and occurs in multiple central nervous system cell types,” the authors wrote. “We identify Rab32, known to increase in response to acute brain inflammation, as a novel unfolded protein response target.

“High Rab32 expression shortens neurite length, alters mitochondria morphology, and accelerates apoptosis/necroptosis of human primary neurons and cells lines.”

Although the authors are unsure why there is an abundance of Rab32 in MS patients, they hypothesize that the defect could originate at the base of the ER organelle.

“Multiple sclerosis can have a devastating impact on people’s lives, affecting mobility, speech, mental ability, and more. So far, all medicine can offer is treatment and therapy for the symptoms—–as we do not yet know the precise causes, research has been limited,” the authors wrote. “Our exciting new findings have uncovered a new avenue for research to explore. It is a critical step, and in time, we hope it might lead to effective new treatments for MS.”

The authors noted that the findings could help scientists develop treatments that target Rab32, and investigate whether other proteins play a role in triggering MS.

“No one knows for sure why people develop MS and we welcome research that increases our understanding of how to stop it,” said Dr David Schley, research communications manager, MS Society. “There are currently no treatments available for many of the more 100,000 people in the UK who live with this challenging and unpredictable condition. We want people with MS to have a range of treatments to choose from, and be able to get the right treatment at the right time.”