It’s only about two weeks ago when GeNeuro’s hopes for a quick win with its HERV-W human endogenous retrovirus program in Multiple Sclerosis experienced a severe blow. Back then, the company had to report that its lead antibody GNbAC1 did not reduce relapse rates in patients with Relapsing Remitting Multiple Sclerosis after six months. HERVs are ancestral retroviral DNA insertions in the human genome, thought to account for up to 8% of the human genome and are believed to have originated from viral infections that were integrated into the human germline during evolution.
Today, GeNeuro announced that preclinical data supporting the role of pathogenic pHERV-W env in Type 1 diabetes has been published in The Journal of Clinical Investigation Insight. As per press release:
These studies show that pHERV-W env has a dual pathophysiological effect in the cascade leading to T1D pathogenesis. A direct effect towards insulin secretion in beta cells is observed, as well as an indirect immune-mediated effect, triggered by the action of pHERV-W env on the TLR4 receptor,” explained Dr. Hervé Perron, Chief Scientific Officer of GeNeuro and one of the authors. “Taken together, these data confirm that neutralizing pHERV-W env is a new therapeutic pathway to explore in T1D. GeNeuro is already conducting a Phase 2a study with GNbAC1, our monoclonal antibody designed to neutralize pHERV-W env.” In the studies, analysis of human T1D samples show that the pHERV-W env protein was found to be expressed in 75% of pancreas samples, detected in 70% of sera and its corresponding RNA was found in 57% of peripheral blood mononuclear cells. In cultures of human Langerhans islets cells, insulin secretion was inhibited by pHERV-W env in a dose-dependent manner.
GeNeuro’s T1D study will read out in H2 2018 so by then we should find out if the failure in MS can maybe be attributed to the blood-brain barrier or if the hypothesis of a pathogenic HERV is a dead end.