GeNeuro

Researchers Detect HERV-W ENV in COVID-19 Patients and Link Expression to Disease Severity - Seite 2

“Our research suggests a genetic and/or epigenetic susceptibility associated to the activation of HERV-W ENV in blood lymphoid cells, which could be important in understanding how SARS-CoV-2 infection may lead to severe forms of COVID-19 in some patients,” said Dr Branka Horvat, who heads the “Immunobiology of Viral infections” team at the International Center Infectiology Research-CIRI. “The findings made in Rome and Lyon, combined with the known pro-inflammatory properties of the HERV-W ENV protein, may shed a new light on the development of severe forms of COVID-19, and may also offer an unforeseen opportunity to stop this evolution through a novel therapeutic approach.”

HERV-W ENV is found in specific disease situations, and its presence is always tied to negative disease outcomes for the patient. The pro-inflammatory effects of HERV-W ENV are mediated through the activation of the TLR4 innate immune receptor, a pathway closely associated with some of the key features of COVID-19, such as hyper-activation of immune functions, endothelial cell activation, vasculitis as well as coagulopathy. To date, HERV-W ENV has mostly been studied in neurodegenerative diseases, with widely observed pathogenic effects on peripheral and central nervous system cells.

“The presence of HERV-W ENV in COVID-19 patients may have a double effect. In the short-term, when activated in genetically susceptible individuals, HERV-W ENV can act as an accelerant to the innate immune response, fueling complications and leading to the need for ventilation. But even after the primary infection is over, if HERV-W ENV has reached a self-fueling expression level, it may cause persistent damage to endothelial cells in blood vessels and also to cells from the peripheral and central nervous system, which could explain many of the long-term neurological symptoms experienced by patients long after SARS-CoV-2 infection,” said Dr. Hervé Perron, Chief Scientific Officer of GeNeuro, who has been working on HERVs for over 30 years.

The link between viral infection and HERV activation in specific diseases has already been well documented. But until now, HERV expression had been observed in limited amounts and mainly found in an affected organ, predominantly in the brain in neurodegenerative disorders. GeNeuro was founded in 2006 as a spin-off of Institut Mérieux to leverage HERV biology into novel treatments by neutralizing pathogenic HERV proteins. Its most advanced drug candidate, temelimab, has shown very promising results in Phase II trials against Multiple Sclerosis (MS), and is presently in a trial against disability progression at the Karolinska Institutet’s Academic Specialist Center (ASC) in Stockholm, Sweden. Temelimab is an anti-HERV-W ENV monoclonal antibody, with demonstrated excellent tolerability and safety in over 400 patient-years of treatment, and is immediately available to study the effects of neutralizing HERV-W ENV in COVID-19 patients.