Forum for Science, Industry and Business

Multiple sclerosis: Endogenous retrovirus HERV-W key to nerve tissue damage

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) affecting brain and spinal cord. In collaboration with colleagues from the USA and Canada, a team of Düsseldorf-based researchers led by Prof. Dr. Patrick Küry from the Department of Neurology has discovered a new way in which nerve tissue is damaged by an endogenous retrovirus.

A microglial cell (green) contacts and attacks a myelinated axon (red). In the presence of the pHERV-W envelope protein, this interaction leads to axonal injury. The blue structures are cell nuclei.

HHU / Joel Gruchot / Patrick Küry

They authors have published their findings in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Early disease stages of MS are primarily characterised by immune cell infiltration of the CNS. This causes inflammation that damages the so-called myelin sheaths. Myelin sheaths are electrically insulating structures established by specialised glial cells of the CNS, referred to as ‘oligodendrocytes’.

These structures protect, nourish and stabilise axons, which transmit electrical signals between neurons.

There is a large therapeutic repertoire of immunomodulatory drugs available that can effectively target the inflammatory aspects of relapsing multiple sclerosis (RMS). But when MS progresses, damage accumulates which ultimately results in irreversible deficits and clinical disability.

Unfortunately, despite decades of intense research disease progression is still untreatable as there are no therapies available that either prevent damage or repair injured axons.

In a new study published online on June 18 in the renowned journal PNAS a research team led by Prof. Dr. Patrick Küry from the Department of Neurology (chaired by Prof. Dr. Hans-Peter Hartung) has shed light on a novel axon damage mechanism which could be highly relevant for progressive MS (PMS) patients.

As outlined by the first author of this research paper, Dr. David Kremer, the envelope (ENV) protein of the pathogenic human endogenous retrovirus type W (pHERV-W) was found to be a major contributor to nerve damage in MS.

In collaboration with research teams in Cleveland (OH, USA) and Montreal (CAN) the authors demonstrated that the ENV protein drives CNS resident microglial cells to contact and damage myelinated axons.

Alongside the scientific research into determining how the damage mechanism works, clinical developments aiming at neutralising the harmful ENV protein in MS patients have also progressed.

Two clinical studies conducted under the supervision of Prof. Hartung have already successfully tested the ENV-neutralising antibody temelimab. MRI scans of the participants treated in the study showed reduced damage to the nerve tissue.

The Düsseldorf-based researchers and their colleagues can therefore explain why neurodegeneration is decreased in patients treated with temelimab. This antibody specifically binds to the ENV protein of the retrovirus and blocks its activity in the CNS.

As stated by Prof. Hartung, future clinical studies in progressive MS patients will now have to demonstrate whether temelimab treatment can also improve clinical symptoms resulting from neurodegeneration.

Originalpublikation:

Kremer D, Gruchot J, Weyers V, Oldemeier L, Göttle P, Healy L, Ho Jang J, Kang T Xu Y, Volsko C, Dutta R, Trapp BD, Perron H, Hartung HP, Küry P., pHERV-W envelope protein fuels microglial cell-dependent damage of myelinated axons in multiple sclerosis, Proc. Natl. Acad. Sci. U. S. A. 2019 Jun 18. pii: 201901283
DOI: 10.1073/pnas.1901283116

Dr.rer.nat. Arne Claussen | idw - Informationsdienst Wissenschaft
Further information:
http://www.hhu.de/

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

Im Focus: Skyrmions like it hot: Spin structures are controllable even at high temperatures

Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...

Im Focus: Making the internet more energy efficient through systemic optimization

Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.

Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.

Im Focus: New synthesis methods enhance 3D chemical space for drug discovery

After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

Im Focus: Quantum fluctuations sustain the record superconductor

Superconductivity approaching room temperature may be possible in hydrogen-rich compounds at much lower pressures than previously expected

Reaching room-temperature superconductivity is one of the biggest dreams in physics. Its discovery would bring a technological revolution by providing...