New study shows how HERV-W contributes to neurodegeneration in MS

GeNeuro, a biopharmaceutical firm dedicated to developing treatments for neurodegenerative and autoimmune conditions like multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and the severe neurological consequences of COVID-19 (post-COVID or long COVID), has recently collaborated with Heinrich-Heine University in Düsseldorf to unveil significant research results regarding the role of HERV-W in MS. These findings have been published in the Proceedings of the National Academy of Science.

Working alongside researchers from Switzerland and France, Prof. Patrick Küry’s team in Düsseldorf, specifically from the Department of Neurology, has made substantial strides in comprehending the intricate disease mechanisms. They’ve established a direct functional link between the release of an endogenous retrovirus and the aggravation of neurodegenerative processes.

Previous studies led by Prof. Patrick Küry’s team hinted at the potential impact of HERV-W on neurodegeneration and the diminished regenerative capacity through oligodendroglial cells—two aspects currently not addressed by approved MS treatments. The latest breakthroughs stemmed from the use of a novel mouse model that mimics HERV-W expression within the central nervous system (CNS).

The research has now successfully demonstrated that W-Env plays a pivotal role in critical MS sub-processes in vivo, including damage to the white matter (myelin) and further impairment of already compromised regeneration capabilities.

Moreover, the presence of aggressive microglial cells has been confirmed, and intriguingly, the emergence of neurotoxic astrocytes has been revealed. These astrocytes, a widespread glial cell population typically engaged in various physiological functions, seem to adopt a primarily neurotoxic nature due to the presence of W-Env in the brain.

Joel Gruchot, from Heinrich-Heine University Düsseldorf’s Neurology department and the lead author of the publication, emphasized that “our study suggests that the presence of W-Env in the brains of MS patients creates a toxic environment. While this data doesn’t definitively establish whether it initiates the MS disease process, it unquestionably showcases how W-Env accelerates degeneration and disrupts the delicate regeneration processes.”

He further noted that “following GeNeuro’s successful clinical trials with its W-Env neutralizing antibody known as Temelimab, we can now elucidate why neurodegeneration notably decreased in MS patients treated with Temelimab: the antibody seems to counteract the ‘toxic’ W-Env protein, preventing its activity within the CNS and the neurotoxic activation of microglia and astrocytes.”

Beyond MS, GeNeuro is also conducting a Phase II clinical trial with Temelimab in long COVID patients, as the activation of W-Env has been detected in the blood of these patients. This discovery may shed light on some of the neurological challenges faced by long COVID sufferers.

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