Manni-Pol Gemelli IRCCS Nerve growth factor in paediatric severe traumatic brain injury: translational and clinical studies on a candidate biomarker and therapeutic drug (DSB.AD007.204)

Area tematica

Scienze biomediche

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di Farmacologia Traslazionale (IFT)

Responsabile di progetto

LUIGI MANNI
Telefono: 0649934248
E-mail: luigi.manni@cnr.it

Abstract

In children, severe traumatic brain injury (TBI) can compromise neurological functions with permanent sequelae including re-perfusion, hypoxia, edema and ischemia. No specific therapy is currently available for TBI-induced neurological deficits. Nerve growth factor (NGF) is a neurotrophin involved in the development and survival of sympathetic, sensory and cholinergic neurons. Several preclinical and clinical evidences indicate NGF as important player in TBI. NGF mRNA in the brain early increases after experimental TBI, parallel to the increase of NGF protein in the CSF and serum. The rise of NGF in the brain and CSF after neurotraumas is directly correlated with those of pro-inflammatory cytokines and the major sources of NGF in TBI experimental models are cells involved in the secondary-phase neuro-inflammation, such as brain resident astrocytes and infiltrating microglia. The mature NGF (mNGF) is the C-terminal fragment of a precursor protein (proNGF) that is produced in two main variants (A and B). The balance between proNGF and mNGF levels in the brain could be a key determinant for brain homeostasis, with its disruption possibly leading to neuronal sufferance.

Obiettivi

This project aims at exploring the value of mNGF, proNGF-A and proNGF-B as biomarkers and therapeutics in children with severe TBI. The project will be structured into two different sub-projects aimed:
1. to study the preclinical pharmacology of proNGF-A in healthy animals and to evaluate the preclinical efficacy of intranasal proNGFs/NGF in THBI animal models;
2. to validate proNGFs/NGF as potential surrogate endpoints in TBI patients.

Data inizio attività

01/01/2020

Parole chiave

Severe Traumatic Brain Injury, Nerve Growth Factor (NGF), pro-Nerve Growth Factor (proNGF);

Ultimo aggiornamento: 28/07/2024