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Article type: Research Article
Authors: Capsoni, Simonaa; b | Covaceuszach, Soniaa; 1 | Ugolini, Gabrielea; 1 | Spirito, Francescaa | Vignone, Domenicoa; b | Stefanini, Barbaraa; 1 | Amato, Gianlucaa; b | Cattaneo, Antoninob; c; *
Affiliations: [a] Lay Line Genomics S.p.A., Rome, Italy | [b] European Brain Research Institute (Foundation EBRI Rita Levi Montalcini), Rome, Italy | [c] International School for Advanced Studies (SISSA), Trieste, Italy
Correspondence: [*] Corresponding author: Prof. Antonino Cattaneo, European Brain Research Institute, Via del Fosso di Fiorano 64/65, 00143 Rome, Italy. Tel.: +39 06501703064; Fax: +39 06501703335; E-mail: [email protected].
Note: [1] Present Address: Rottapharm Biotech srl, Area Science Park edificio Q1, 34012 Basovizza-Trieste, Italy.
Abstract: Nerve growth factor (NGF) has a great potential for the treatment of Alzheimer's disease. However, the therapeutic administration of NGF represents a significant challenge, due to the difficulty to deliver relevant doses to the brain, in a safe and non-invasive way. We previously demonstrated the efficacy of a non-invasive delivery of NGF to the brain in animal models, by an intranasal route. Recently, topical eye application of NGF was proposed, as an option for the delivery of NGF to the brain. Here, we compare the efficacy of the two delivery routes of hNGF-61, a recombinant traceable form of human NGF, in the mouse neurodegeneration model AD11. The intranasal administration appeared to be significantly more effective than the ocular one, in rescuing the neurodegenerative phenotypic hallmarks in AD11 mice. The ocular administration of hNGF-61 showed a more limited efficacy, even at higher doses. Thus, NGF nasal drops represent a viable and effective option to successfully deliver therapeutic NGF to the brain in a non-invasive manner.
Keywords: Alzheimer's disease, delivery, dosage, intranasal, nerve growth factor, non-invasive, ocular, pharmacokinetic, side effects, therapeutic window
DOI: 10.3233/JAD-2009-0953
Journal: Journal of Alzheimer's Disease, vol. 16, no. 2, pp. 371-388, 2009
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