Innovating Works

OpiO

Financiado
Opioids and insulin secretion: a new avenue to fight type 2 diabetes
Type 2 diabetes (T2D) and obesity are leading causes of morbidity and mortality, becoming a major burden on public health. Failure to understand their pathophysiology has frustrated efforts to develop improved therapeutic strategi... Type 2 diabetes (T2D) and obesity are leading causes of morbidity and mortality, becoming a major burden on public health. Failure to understand their pathophysiology has frustrated efforts to develop improved therapeutic strategies. T2D and obesity are complex polygenic disorders. Genome-wide association studies have identified hundreds of loci associated with metabolic traits, but they have not led to promising new drug targets, so far. In contrast, the identification and characterization of rare mutations causing monogenic metabolic disorders have been instrumental in repositioning or developing drugs. Beyond this proof of concept, the challenge is to use genomic medicine for innovative molecules restoring impaired insulin secretion that characterizes T2D. OπO has stemmed from the old but forgotten correlation between opioids consumption and metabolic trait abnormalities. Opioids classically act through delta opioid receptor (DOP encoded by OPRD1), kappa and mu opioid receptors. Based on my preliminary data that include large-scale human functional genetics of OPRD1 mutations, my hypothesis is that DOP is a major link between opioids and metabolism in humans. More specifically, I propose that DOP and opioid signaling have a crucial direct role in insulin secretion from pancreatic β cells; making DOP a promising new drug target against T2D. In this context, I suggest four tasks in OπO: the first two tasks will decipher the role of DOP and opioid signaling in metabolism with a specific focus on islets and β cells, while the two following tasks will decipher the systemic contribution of opioids and opioid receptors to metabolism. The methodologies that I proposed are truly comprehensive and innovative as they combine preclinical animal studies (with a humanized mouse model), deep phenotyping of islets, pharmacology, multi-omic analyses, genome editing, functional genetics, genetic epidemiology (including Mendelian randomization) and clinical intervention study. ver más
30/09/2027
INSERM
2M€
Perfil tecnológico estimado
Duración del proyecto: 63 meses Fecha Inicio: 2022-06-08
Fecha Fin: 2027-09-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-06-08
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2021-COG: ERC CONSOLIDATOR GRANTS
Cerrada hace 3 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5