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Associative mechanisms linking a defective minipuberty to the appearance of mental and nonmental disorders: infantile NO replenishment as a new therapeutic possibility

Project description

For better treatment of those born prematurely

Individuals born prematurely not only face increased risks as newborns but also suffer from multimorbidity in their later life. This is associated with adaptive changes of the hypothalamic-pituitary-gonadal axis during infancy, but the exact mechanisms underlying its malfunction and its consequences are largely unknown. The EU-funded miniNO project will conduct out pioneering research on the connection between alterations in minipuberty and infantile nitric oxide (NO) signaling in the brain, and comorbidities that appear later in life in prematurely born individuals. The project is based on previous clinical studies and solid data of the collaborating teams. It will create an extensive repertoire of clinical and genetic data, associating minipuberty and brain NO levels with mental and non-mental disorders, having as its main aim the search for explanations and treatments for the health burdens of millions of prematurely born people.

Objective

The miniNO project aims to identify the key causative mechanisms of the lifelong multimorbidity associated with preterm birth. Prematurity is associated with alterations in the maturation of the hypothalamic-pituitary-gonadal axis, and specifically with its transient activation during infancy, known as minipuberty. miniNO will study for the first time the association between premature birth and alterations in minipuberty and infantile nitric oxide (NO) signaling in the brain, and comorbidities that appear later on in life. The project is based on robust preclinical data and previous clinical studies, and will exploit data concerning premature birth and minipuberty in existing cohorts as well as newly created cohorts. We will identify the molecular association between NO deficiency, altered minipuberty and multimorbidity combining mental (e.g. autism, social cognition, learning and memory impairments) and non-mental disorders (e.g. anosmia, hearing loss, metabolic abnormalities, cardiovascular impairements and infertility) as well as gender, environmental and lifestyle factors. For this, we have assembled a unique interdisciplinary consortium of renowned basic scientists (neuroscientists) and clinicians (pediatric and adult endocrinologists, psychiatrists, geneticists) and an SME to implement the project results. By validating the causative mechanisms of the multimorbidity related to preterm birth, we will propose and develop novel diagnostic and preventive tools, including screening tests for biomarkers and newly identified genetic factors, for altered minipuberty, thus paving the way to personalized treatment and new therapeutic options very early in life. miniNO is expected to improve the quality of life of millions of prematurely born individuals and reduce the financial and societal burdens they impose.

Call for proposal

H2020-SC1-BHC-2018-2020

See other projects for this call

Sub call

H2020-SC1-2019-Two-Stage-RTD

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 943 750,00
Address
RUE DE TOLBIAC 101
75654 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
€ 943 750,00

Participants (12)