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Updated: Jul 15, 2025
Intranasal Administration of CNS Therapeutics to Awake Mice
Published on: April 8, 2013
Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive
Antonio Gatto1, Lavinia Capossela2, Giorgio Conti3
1Dipartimento di Pediatria, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
Insights
Intranasal human-recombinant Nerve Growth Factor (hr-NGF) shows promise in improving neurological and clinical outcomes for children with unresponsive wakefulness syndrome after severe traumatic brain injury (TBI). This treatment facilitated recovery of brain function and reduced spasticity without reported side effects.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Regenerative Medicine
Background:
- Severe traumatic brain injury (TBI) in children has a low survival rate and often leads to long-term neurological and behavioral sequelae, including unresponsive wakefulness syndrome (UWS).
- Current treatments for severe TBI in children are limited in their ability to restore neuronal loss or significantly improve outcomes.
- Human-recombinant Nerve Growth Factor (hr-NGF) has demonstrated neuroprotective and neuro-regenerative properties in animal models, supporting neuronal growth, differentiation, survival, and neurogenesis.
Purpose of the Study:
- To evaluate the efficacy of intranasal human-recombinant Nerve Growth Factor (hr-NGF) administration in pediatric patients diagnosed with post-traumatic unresponsive wakefulness syndrome (UWS).
- To assess the impact of hr-NGF treatment on neuronal function recovery and clinical improvement in children with severe TBI sequelae.
Main Methods:
- Three pediatric patients with post-traumatic UWS received intranasal hr-NGF at a total dose of 50 gamma/kg, administered three times daily for 7 consecutive days, over 4 monthly cycles.
- Neuroradiological assessments included Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) scans.
- Electrophysiological evaluations involved Electroencephalography (EEG) and Power Spectral Density (PSD) analysis.
- Neurological status was assessed using the modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale.
Main Results:
- Intranasal hr-NGF administration led to improvements in functional brain imaging (PET, SPECT) and electrophysiological assessments (EEG, PSD).
- Patients exhibited clinical improvements, including reduced spasticity, acquisition of voluntary movements, improved facial mimicry, attention, verbal comprehension, and feeding capacity.
- Significant improvements were observed in neurological scores, with no adverse side effects reported during the treatment period.
Conclusions:
- Intranasal hr-NGF administration demonstrated promising results in improving neurological function and clinical status in children with post-traumatic UWS.
- The ease of administration and positive outcomes suggest that hr-NGF warrants further investigation, particularly in early stages post-TBI and in patients with better baseline neurological conditions.
- This approach holds potential for enhancing neuronal recovery following traumatic brain damage in pediatric populations.
Background:
Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS.
Methods:
Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale.
Results:
Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported.
Conclusion:
These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.
