New Study Published in PNAS Further Substantiates the Neuropathogenic Role of the HERV-W Protein in MS
September 27 2023 - 1:30AM
Business Wire
- Publication of data from novel mouse models mimicking
expression of HERV-W in the central nervous system.
- Data confirms that the expression of the HERV-W Env protein
(W-Env) causes a neurodegenerative environment, through the
fostering of demyelination and the reduction of remyelination,
which may explain the long-term neurodegeneration suffered by MS
patients.
- The study has been published in the journal “Proceedings of the
National Academy of Sciences of the United States of America”
(PNAS), resulting from a collaboration between the Heinrich-Heine
University in Düsseldorf, research teams from the Universities of
Zürich and Bern with GeNeuro.
The article is available for consultation at the following link:
https://www.pnas.org/doi/10.1073/pnas.2308187120
Regulatory News:
GeNeuro (Euronext Paris: CH0308403085 - GNRO), a
biopharmaceutical company developing treatments for
neurodegenerative and autoimmune diseases, such as multiple
sclerosis (MS), amyotrophic lateral sclerosis (ALS) and the severe
neuro-psychiatric consequences of COVID-19 (post-COVID or
Long-COVID), today announced, in collaboration with the
Heinrich-Heine University in Düsseldorf, the publication in the
leading scientific publication PNAS of results from their joint
research on the role of HERV-W in MS.
In collaboration with colleagues from Switzerland and France,
the Düsseldorf research team led by Prof. Patrick Küry (Department
of Neurology) made important progress in understanding the complex
disease mechanism by describing a direct functional connection
between the release of an endogenous retrovirus and the worsening
of neurodegenerative processes.
Previous studies by Prof. Patrick Küry's team were able to
demonstrate a possible influence of HERV-W on neurodegeneration and
on the reduction of the regeneration capacity (via oligodendroglial
cells) - two processes that are not addressed by approved drugs to
treat MS. The new findings by this team resulted from the use of a
novel mouse model that mimics the expression of HERV-W in the
central nervous system (CNS).
The research has now been able to prove that W-Env is indeed
involved in important MS sub-processes in vivo: damage to the white
matter (myelin) and a further weakening of the already impaired
regeneration capacity. In addition, the occurrence of aggressive
microglial cells was confirmed and, surprisingly, the generation of
neurotoxic astrocytes was revealed. This is a widespread glial cell
population that is naturally involved in many physiological
functions, but which, as a result of the presence of W-Env in the
brain, now appears to acquire a primarily neurotoxic character.
“Our study shows that the presence of W-Env in the brains of MS
patients appears to generate a toxic environment. It cannot be
determined from this data whether this actually initiates the MS
disease process, because the model we used is not suitable for
this. However, it has now been clearly demonstrated for the first
time that the W-Env increases the decay processes and disrupts the
sensitive regeneration processes”, said Joel Gruchot, from the
Heinrich-Heine-University Düsseldorf’s department of Neurology and
lead author of the publication. He added that “after GeNeuro’s two
clinical studies with its W-Env neutralizing antibody called
Temelimab, we can now explain why neurodegeneration successfully
decreased in MS patients treated with Temelimab: the antibody
appears to neutralize the “toxic” W-Env protein and thus prevents
its activity in the CNS as well as the neurotoxic activation of
microglia and astrocytes.
In addition to MS, GeNeuro is also testing Temelimab in a Phase
II clinical trial in Long-COVID patients, as activation of W-Env is
measured in the blood of affected patients, which may explain some
of the neurological deficits suffered by these patients.
About GeNeuro
GeNeuro's mission is to develop safe and effective treatments
for neurological disorders and autoimmune diseases, such as
multiple sclerosis, by neutralizing the causative factors encoded
by HERVs, which represent 8% of human DNA.
GeNeuro is headquartered in Geneva, Switzerland, and has R&D
facilities in Lyon, France. It has rights to 18 patent families
protecting its technology.
For more information, please visit: www.geneuro.com
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