MedicalResearch.com Interview with:
Sandrine Levet PhD
Preclinical Study Manager
MedicalResearch.com: What is the background for this study?
Response: Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W Env) has been involved in multiple sclerosis pathogenesis.
A previous study published in JCI Insight revealed that HERV-W Env is also involved in Type 1 diabetes (T1D) pathogenesis. In this study, we observed that HERV-W-Env protein and RNA are detected respectively in sera and peripheral blood mononuclear cell (PBMC) of T1D patients.
We also demonstrated that this pathogenic protein is expressed by acinar cells in human T1D pancreas and is associated with the recruitment of macrophages within the pancreas of these patients. HERV-W Env also displays direct pathogenic properties as it inhibits insulin secretion by human islets of Langerhans.
MedicalResearch.com: What are the main findings?
Response: In this new study we demonstrated that mice expressing pHERV-W Env are prone to develop symptoms relevant for Type 1 diabetes following environmental insult targeting beta-cells.
Normal and transgenic mice (in which pHERV-W Env is expressed) were given streptozotocin, a toxic molecule known to induce experimental diabetes. Following streptozotocin exposure, transgenic mice were found to be much more susceptible to pancreatic damage than wild-type mice as they developed severe insulitis (P < 0.0001) and hyperglycemia (P < 0.01). Moreover, pHERV-W Env transgenic mice displayed severe pancreatic abnormalities that could explain their elevated susceptibility to streptozotocin.
MedicalResearch.com: What should readers take away from your report?
Response: The evidence that pHERV-W Env plays a role in the pathogenesis of Type 1 diabetes is growing. If these transgenic mice results can be translated into humans, a potential new avenue of therapy could open for patients expressing this pathogenic protein.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: At GeNeuro, we have already started a clinical study targeting pHERV-W Env in T1D. Patient enrolment in an Australian Phase 2a study of GNbAC1 has been completed on schedule and initial 6-months results are expected in September 2018.
The Phase 2a randomized, placebo-controlled study is evaluating GNbAC1 in 60 recently diagnosed adult patients in over 10 centers in Australia. The primary endpoint is the safety of GNbAC1 in this new population of patients. Secondary endpoints will measure the link between treatment response and pHERV-W Env biomarkers, insulin production based on peptide C levels, and other biomarkers associated with type 1 diabetes, such as insulin consumption, glycaemia and production of diabetic auto-antibodies.
Disclosures: Disclosures: S. Levet: Employee; Self; Geneuro Innovation
 Levet S et al. An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes. JCI Insight 2017, 2(17):e94387.
2018 ADA abstract:
HERV-W-Env Involvement in Human T1D Pathogenesis—New Insights from Two Mouse Models
SANDRINE LEVET, JULIE JOANOU, NELLY QUERUEL, JUSTINE PIERQUIN, HERVE J.F. PERRON, Lyon, France
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