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Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma

Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromis...

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Autores principales: Manni, Luigi, Conti, Giorgio, Chiaretti, Antonio, Soligo, Marzia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635100/
https://www.ncbi.nlm.nih.gov/pubmed/34867367
http://dx.doi.org/10.3389/fphar.2021.754502
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author Manni, Luigi
Conti, Giorgio
Chiaretti, Antonio
Soligo, Marzia
author_facet Manni, Luigi
Conti, Giorgio
Chiaretti, Antonio
Soligo, Marzia
author_sort Manni, Luigi
collection PubMed
description Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson’s disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain.
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spelling pubmed-86351002021-12-02 Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma Manni, Luigi Conti, Giorgio Chiaretti, Antonio Soligo, Marzia Front Pharmacol Pharmacology Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson’s disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain. Frontiers Media S.A. 2021-11-16 /pmc/articles/PMC8635100/ /pubmed/34867367 http://dx.doi.org/10.3389/fphar.2021.754502 Text en Copyright © 2021 Manni, Conti, Chiaretti and Soligo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Manni, Luigi
Conti, Giorgio
Chiaretti, Antonio
Soligo, Marzia
Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma
title Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma
title_full Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma
title_fullStr Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma
title_full_unstemmed Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma
title_short Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma
title_sort intranasal delivery of nerve growth factor in neurodegenerative diseases and neurotrauma
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635100/
https://www.ncbi.nlm.nih.gov/pubmed/34867367
http://dx.doi.org/10.3389/fphar.2021.754502
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