The data presented considerable evidence that the pathogenic protein envelope (Env) of HERV-W could be a causative factor of diabetes type 1
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Significant Expression of the pathogenic protein HERV-W-Env, found in the pancreas of more than 50% of patients with type 1 diabetes
GNbAC1, a humanized monoclonal antibody targeting the protein of HERV-W-Env, which is currently in phase II study in type 1 diabetes
Geneva, Switzerland, on June 12, 2017 7: 30 am CEST GeNeuro SA (Euronext Paris : CH0308403085 GNRO), a biopharmaceutical company that develops new treatments against autoimmune diseases, such as multiple sclerosis or type 1 diabetes, today announced data supporting the link between human endogenous retroviruses (HERVS) and type 1 diabetes (T1D). The data were presented at the 77es scientific sessions of the American Diabetes Association in San Diego, the United States, from 9 to 13 June 2017.
The HERVS are genetic elements proviraux ancestral, which currently, it is estimated that they account for 8% of the human genome. Most of the HERVS are repressed, however, in some sensitive individuals, in pathological conditions, they may be transactivés and the viral proteins that result appear to play a causative role in many autoimmune diseases and neurodegenerative disorders.
“Our data presented at the congress of the ADA 2017 support the involvement of the pathogenic protein HERV-Env in the recruitment of immune cells inside the pancreas of patients with type 1 diabetes and transgenic mice, leading to a reduction in insulin levels in the blood,” said Hervé Perron, Director of scientific affairs at GeNeuro.
“It is also interesting to note that the activation of the pathogenic protein HERV-W Env in human cells can be triggered by infections with enteroviruses, such as certain strains of Coxsackievirus B4. GeNeuro is in phase II clinical development with GNbAC1, its humanized monoclonal antibody designed to neutralize this protein, both in multiple sclerosis and in type 1 diabetes.”
The analyses and immuno-histological findings of the pancreas of patients with T1D have shown that the expression of HERV-W was correlated with infiltrates of macrophages (p < 0.01) and combined independently with infiltrates of lymphocytes T. In vitro, the protein HERV-W-Env directly inhibited insulin secretion induced by glucose in human beta cells in culture in a dose-dependent manner. In a murine transgenic model with the pathogenic protein
HERV-W-Env, the immune cell infiltrates were found in the pancreas (p < 0.01), with resulting hyperglycemia important and a reduction of insulin secretion.
The data obtained on cells Hep2 human infected by the Coxsackievirus (strain CV-B4E2) isolated in the pancreas in T1D have shown an up-regulation of the significant increase in the transcription of the Mrna of the protein of HERV-W-Env when compared to uninfected cells (p < 0.001 at an MOI = 10-2 ; p < 0.05, a I = 10-5). This effect was not observed with strain CV-B4 (non-isolated in the pancreas in T1D), suggesting a specific effect of the strain.
About the study evaluating GNbAC1 in type 1 diabetes
The study, Phase IIa, randomized, placebo-controlled trial is designed to evaluate the safety of GNbAC1 in 60 adult patients, with newly diagnosed. The secondary endpoints will be measures of the link between treatment response and biomarkers of HERV-W Env. The response to treatment will be assessed by measurements of insulin production based on the rate of C-peptide, consumption of insulin, the blood sugar levels and the production of antibodies directed against the beta cells in the pancreas. The recruitment of the last patient is planned for the end of 2017 and the results of the study are expected in the third quarter of 2018.
About type 1 diabetes
Type 1 diabetes, usually diagnosed in children, is due to an immune response directed against the beta cells, producing insulin in the pancreas. There is no treatment for this disease ” auto-immune “, which means that it requires insulin therapy for life. However, this treatment is often associated with disabling complications, such as heart failure, renal and blindness.
About the GNbAC1
The development of GNbAC1 is the result of 25 years of research on human endogenous retroviruses (HERV), of which 15 years within the Institut Mérieux and INSERM, before the creation of GeNeuro in 2006. Present in the human genome, some HERVS have been associated with various autoimmune diseases. The researchers demonstrated that the toxic protein Approx end of MSRV (Multiple Sclerosis RetroVirus) found in patients with multiple sclerosis and in particular at the level of active lesions, promotes inflammatory processes via interaction with TLR4 in the innate immunity and block the remyelination of neurons. By neutralizing MSRV-Env, GNbAC1 could all at once oppose these inflammatory processes in pathological conditions and to restore the process of remyelination. The protein MSRV-Env, having no physiological function known, GNbAC1 has a good safety profile, with no effect on the immune system of the patient, as has been demonstrated in all the clinical studies conducted to date.
The mission of GeNeuro is developing treatments both safe and effective against neurological disorders, and autoimmune diseases, such as multiple sclerosis, neutralizing the causal factors induced by the human endogenous retroviruses (HERVS) constitute 8% of the human genome.
Based in Geneva, Switzerland, with R&D centers in Archamps, in Haute-Savoie and Lyon, GeNeuro has 31 employees. It holds the rights to 16 families of patents that protect its technology.
For more information, please visit : www.geneuro.com
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