GeNeuro presents data supporting pathogenic role of an endogenous retroviral protein (HERV-W ENV)
in post-COVID neuropsychiatric syndrome and enters collaboration with the FondaMental Foundation to speed development of diagnostic and therapeutic options for patients.
GeNeuro (Euronext Paris: CH0308403085 - GNRO), a biopharmaceutical company developing new treatments for neurodegenerative and autoimmune diseases, such as multiple sclerosis (MS), presented new data showing that the neuropsychiatric symptomatology seen in “post-COVID” patients may be due to activation of HERV-W ENV expression in these individuals by SARS-CoV-2, and to its persistence long after the acute COVID phase. These data, presented at the first “Neuro Sciences Psychiatry and Neurology Days” held in Paris, France, on July 1-2, provide a biologic rationale explaining why so many COVID-19 patients develop long-term neurological and psychiatric symptoms. This could open the door for a therapeutic intervention with temelimab targeting HERV-W ENV.
According to recent large-scale studies, more than 10% of people infected by SARS-CoV-2 fail to fully recover and/or develop new symptoms, with a high proportion of neurological and/or psychiatric affections. Of note, in more than 90% of the cases the original COVID-19 symptoms were not severe enough to warrant hospitalization. With more than 176 million confirmed COVID-19 cases worldwide, of which more than 80 million in the USA and Europe, this problem is now being recognized as a major public health emergency, as it could affect millions of persons.
“We are confronted with a wave of depressive and cognitive disorders occurring sometimes several months after a COVID-19 infection, regardless of the severity of their acute phase,” said Prof. Marion Leboyer, Head of Psychiatry at Henry Mondor University Hospitals (Paris Est Creteil University) and Director of the FondaMental Foundation. “Previous publications have established a link between the occurrence of psychotic disorders in patients carrying markers of inflammation and the envelope protein of the endogenous human retrovirus (HERV-W ENV). Finally, preliminary data have shown a significant increase in the levels of this HERV-W ENV protein in post-COVID patients presenting neuropsychiatric symptoms. This finding, which we will test on a large cohort of patient samples, could be a key element in understanding the problem and opening up treatment options.”
Recent publications have shown that expression of HERV-W ENV was triggered by SARS-CoV-2 in vitro in white blood cells of approximately 20% of healthy donors, suggesting individual susceptibility. This protein was also detected in the blood of hospitalized COVID-19 patients where the amount of expression in lymphocytes was associated with the severity of disease progression.
The data presented by Dr. Hervé Perron, CSO of GeNeuro, at the conference reveal that upon infection with COVID-19, HERV-W ENV expression can also be triggered in the brain, specifically in microglial cells that are also innate immune cells residing in the brain. The expression of HERV-W ENV in this organ had previously only been observed in the context of chronic neurological diseases, such as multiple sclerosis or certain inflammatory forms of schizophrenia, where it fuels local inflammation and neurodegenerative mechanisms. In the aftermath of COVID-19, the analysis of preliminary data from patients with post-COVID depressive and/or cognitive disorders now also shows the persistence of HERV- W ENV in the blood.
Under the umbrella of and with funding from the FondaMental Foundation, Prof Leboyer has federated leading European university neuropsychiatric hospitals in France, Belgium and Italy to assemble a cohort of over 300 samples from post-COVID patients with neuropsychiatric disorders, which will be analyzed this summer for HERV-W ENV and inflammatory biomarkers at the INSERM “We-Met" laboratory of the University of Toulouse. “Our objective is to quantify more precisely the link between these biomarkers and the depressive and cognitive disorders suffered by post-COVID patients, in order to pave the way for what would be one of the first diagnostic and therapeutic approaches in this indication,” said Prof. Leboyer.
GeNeuro’s most advanced drug candidate, temelimab, has been developed to neutralize HERV-W ENV and may offer a first therapeutic option for patients affected by post-COVID neuropsychiatric syndromes. Temelimab has shown very promising results in Phase II trials against MRI markers of neurodegeneration in MS, with excellent safety and tolerability in more than 200 patients treated for 2 years or more.
“Post-COVID is emerging as a key global health issue following COVID-19 infection,” stated Jesús Martin-Garcia, CEO of GeNeuro. “We thank Prof. Leboyer and her academic partners for their fast, generous and thorough reaction to the post-COVID crisis and if, as we expect, the analysis of these large- cohorts confirms the result of the pilot studies, we are committed to conduct a clinical trial with these partners to offer patients a therapeutic option against these highly disabling conditions.”