A Translational Psychiatry publication indicates that SARS-CoV-2 infection, even when unnoticed or asymptomatic, can have an influence on the activation of the Human Endogenous Retrovirus W (W-ENV) protein in psychotic patients, in a context of innate immune inflammation.
GeNeuro, a biopharmaceutical company developing treatments for neurodegenerative and autoimmune diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and the severe neuro-cognitive consequences of Covid-19 (post-Covid or Long Covid), published this study in collaboration with Professor Marion Leboyer from the FondaMental Foundation and Dr Ryad Tamouza, Head Immunologist for the immuno-psychiatry team.
The study shows that over 80% of the patients hospitalised in a psychiatry department near Paris during the first wave of the Covid-19 pandemic had been exposed to SARS-CoV-2, which was 1.6 times more than the control group.
27% of patients with non-vaccinal SARS-COV-2 positive serology corresponded to the previously described psychotic disorder subgroup associating HERV-W expression. These results are compared to those of a recent study, which has shown showing that the SARS-CoV-2 virus causing Covid-19 can trigger the activation of the HERV-W retrovirus, which may result in post-infectious syndromes or diseases associated with persistent HERV-W ENV expression in genetically predisposed individuals.
Several specific factors explaining asymptomatic or unrecorded Covid-19 in these in-patients, hospitalised in the Psychiatry Department of the Créteil-Paris VII university hospital in France, have also been suggested.
The authors conclude that this now well-deﬁned subgroup of “inflammatory psychoses” calls for the development of a differential therapeutic approach in psychoses and, more specifically, the identification and development of further HERV-related precision medicine therapies.
Targeting HERV-W ENV
GeNeuro has initiated a programme with its main therapeutic asset, temelimab (an antibody targeting HERV-W ENV), in Long Covid for patients with persistent neurological and neurocognitive symptoms. At the end of 2022, the company launched GNC-501, a Phase II trial evaluating the clinical efficacy of a six-month treatment with temelimab on the improvement of cognitive impairment and/or fatigue in Long Covid patients who are positive for the presence of W-ENV protein in their blood.
The first months of the trial have already confirmed that the W-ENV protein is present in the blood of over 25% of patients with persistent syndromes who suffered from Long Covid. Positive results from this ongoing clinical trial could offer a therapeutic solution through a personalised medicine approach to a large and well-identified subset of millions of patients affected by Long Covid.
“Our study shows a dominant prevalence of unnoticed SARS-CoV-2 infection in patients hospitalised in our psychiatric department during the first wave of the Covid-19 pandemic. This is found to be associated with psychotic patients presenting both immunoinflammation and W-ENV protein expression, a subgroup that we had characterised in a previous pre-pandemic study,” said Dr Ryad Tamouza, Head Immunologist for the immuno-psychiatry team at the Mondor Hospital (Université Paris Est Créteil) in Paris and lead author of the publication.
“The results strongly advocate for a precision medicine strategy targeting this W-ENV protein in these patients with post-infectious and immunoinflammatory profiles,” added Professor Marion Leboyer, Director of the Department of Psychiatry at Henri Mondor University Hospitals (Université Paris Est Créteil) and Director of the FondaMental Foundation.
“This study paves the way for the biomarker identification of patients’ subgroups within a clinically defined nosological entity, who can be efficiently treated with a relevant and targeted therapeutic approach. With this, a precision medicine approach, GeNeuro is bringing a real innovation in the treatment of Long Covid with an ongoing Phase II clinical trial,” said Dr Hervé Perron, Chief Scientific Officer of GeNeuro.