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Neurofunctional and Clinical Effects of Intranasal Human Recombinant Nerve Growth Factor in Children with Acquired
Lorenzo Di Sarno1, Serena Ferretti1, Lavinia Capossela1
1Dipartimento di Pediatria, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy.
Insights
Intranasal human recombinant nerve growth factor (hr-NGF) shows promise for pediatric brain injuries like TBI and HIE. This safe treatment may improve neurorepair and functional recovery, supporting future multimodal therapies.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Pediatric Neurology
Background:
- Pediatric traumatic brain injury (TBI) and hypoxic-ischemic encephalopathy (HIE) lead to significant disability via complex secondary injury pathways.
- Nerve growth factor (NGF) offers neuroprotective and restorative benefits, but effective delivery methods are crucial for pediatric applications.
- Intranasal delivery of human recombinant NGF (hr-NGF) presents a non-invasive strategy to target brain repair in pediatric neurodevelopmental disorders.
Purpose of the Study:
- To review preclinical and clinical evidence on the efficacy and safety of intranasal hr-NGF for pediatric TBI and HIE.
- To assess the potential of intranasal hr-NGF as an adjunct therapy for enhancing neurorepair and functional outcomes.
- To identify the need for further research, including randomized controlled trials, to optimize treatment protocols.
Main Methods:
- A systematic literature search adhering to PRISMA guidelines was performed across major databases (Scopus, PubMed, Cochrane CENTRAL) from 2000 to 2025.
- Keywords included "intranasal NGF", "TBI", "HIE", and "pediatric" to identify relevant preclinical models and clinical case studies.
- Study selection focused on pediatric patients with brain injuries receiving NGF, with outcome assessment via clinical scales, neuroimaging, or electroencephalography (EEG).
Main Results:
- Preclinical studies demonstrated that intranasal NGF reduced lesion volume, inflammation, and neurological deficits, while enhancing angiogenesis and cholinergic function.
- Clinical observations in pediatric patients with meningitis, TBI, and HIE showed improvements in consciousness, motor function, cognition, and brain perfusion.
- No adverse events were reported in relation to intranasal hr-NGF administration, indicating a favorable safety profile.
Conclusions:
- Intranasal hr-NGF appears to be a safe and effective method for reactivating neural plasticity in pediatric brain injury.
- Observed improvements in motor, cognitive, and neurophysiological functions suggest potential benefits for long-term recovery.
- Further rigorous investigation through randomized controlled trials is essential to confirm efficacy and establish optimal treatment strategies for multimodal therapeutic approaches.
Abstract:
Background: Traumatic brain injury (TBI) and hypoxic-ischemic encephalopathy (HIE) cause significant pediatric morbidity through primary insults and secondary cascades like excitotoxicity, neuroinflammation, and impaired plasticity. Nerve growth factor (NGF) promotes neuroprotection, anti-inflammation, and repair, but delivery challenges persist. This review evaluates preclinical and clinical evidence on intranasal human recombinant NGF (hr-NGF) to enhance neurorepair in pediatric TBI and HIE patients. It aims to clarify the potential of intranasal hr-NGF as part of future multimodal approaches to enhance brain repair and improve functional recovery across the lifespan. Methods: A PRISMA-guided literature search (2000-2025) was conducted across Scopus, PubMed, and Cochrane CENTRAL using terms like "intranasal NGF", "TBI", "HIE", and "pediatric". Eligible studies involved pediatric brain injury patients receiving NGF, with outcomes via clinical scales, imaging, or EEG. Results: Preclinical models showed that intranasal NGF reduces lesion volume, inflammation, and deficits while boosting angiogenesis and cholinergic function. Clinically, one child with meningitis and five TBI cases exhibited improved consciousness, spasticity, motor scores, cognition, and brain imaging. Three HIE cases gained voluntary movements, expressivity, and perfusion. No adverse events occurred related to hr-NGF administration. Conclusions: Intranasal hr-NGF safely reactivates plasticity in pediatric brain injury, yielding motor, cognitive, and neurophysiological gains. Preliminary data support multimodal use, but randomized trials are needed to optimize protocols and confirm efficacy.
