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

ongoing

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.