Background:Nerve growth factor (NGF) is known for playing a critical protective role on a number of brain neurons in mammals, including humans. NGF can be delivered to the CNS via nasal route and has a neuroprotective action in case of neurodegenerative diseases.Objective:The aim of this study is to investigate for the first time whether purified NGF can play a neuroprotective role on human brain neurons affected by neurodegenerative diseases when administered via nasal route.Methods:Two female patients, both affected by frontotemporal dementia (FTD) associated with corticobasal syndrome (CBS) at different stages of disease progression, received a daily intranasal NGF spray for one year. Clinical/neurological aspects were observed over time. The follow-up study was performed using 18 FDG PET.Results:This case study seems to demonstrate that IN-NGF slows down the common decline caused by FTD/CBS.Conclusions:These findings suggest the potential neuroprotective role of IN-NGF administered in case of neurodegenerative diseases.

The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an increased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deficits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

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spinal cord injury alters a number of endogenous biological signals known to be involved in the modulation of neurotrophic and neuroprotective events. nerve growth factor (ngF) is a neurotrophic factor expressed in neuronal and non-neuronal tissues including spinal cord, and increases after spinal cord injury. Recent findings revealed that leptin, an adipocyte-derived cytokine (adipokine), enhance neuronal survival and exert neuroprotective action, and played an important role in nociceptive behavior induced by nerve injury. Whether ngF affects the expression of leptin in injured spinal cord has not been investigated. The present study was designed to evaluate: (i) whether intranasal ngF administration reached the spinal cord of the rat, (ii) if ngF affects the expression of leptin in the spinal cord and adipose tissue, and (iii) whether intranasal ngF affects the behavioral and spinal cord neuronal deficits induced by spinal cord injury. The result showed that intranasal ngF enhances the expression of (i) ngF and ngF-receptors (Trka and p75 nTR) in injured spinal cord exerting behavioral and neuroprotective action, and (ii) leptin in injured spinal cord and in subcutaneous (white) and interscapular (brown) adipose tissue. altogether, the present data demonstrate the efficacy of intranasal administration of ngF, and suggest a link between the neurotrophin ngF and the adipokine leptin that may be therapeutically explored in injured spinal cord.