Delivery of NGF to the brain: intranasal versus ocular administration in anti-NGF transgenic mice.
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.
Capsoni
Simona
S
Lay Line Genomics S.p.A., Rome, Italy.
Covaceuszach
Sonia
S
Ugolini
Gabriele
G
Spirito
Francesca
F
Vignone
Domenico
D
Stefanini
Barbara
B
Amato
Gianluca
G
Cattaneo
Antonino
A
D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008845:Microinjections; D016296:Mutagenesis; D020932:Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D010364:Pattern Recognition, Visual / Q000187:drug effects; D013997:Time Factors
D000911:Antibodies, Monoclonal; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase