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Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets.
Proc. Natl. Acad. Sci. U.S.A. 120:e2200057120 (2023)
Antibody delivery to the CNS remains a huge hurdle for the clinical application of antibodies targeting a CNS antigen. The blood-brain barrier and blood-CSF barrier restrict access of therapeutic antibodies to their CNS targets in a major way. The very high amounts of therapeutic antibodies that are administered systemically in recent clinical trials to reach CNS targets are barely viable cost-wise for broad, routine applications. Though global CNS delivery of antibodies can be achieved by intrathecal application, these procedures are invasive. A non-invasive method to bring antibodies into the CNS reliably and reproducibly remains an important unmet need in neurology. In the present study, we show that intranasal application of a mouse monoclonal antibody against the neurite growth-inhibiting and plasticity-restricting membrane protein Nogo-A leads to a rapid transfer of significant amounts of antibody to the brain and spinal cord in intact adult rats. Daily intranasal application for 2 wk of anti-Nogo-A antibody enhanced growth and compensatory sprouting of corticofugal projections and functional recovery in rats after large unilateral cortical strokes. These findings are a starting point for clinical translation for a less invasive route of application of therapeutic antibodies to CNS targets for many neurological indications.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Nogo-a ; Antibody Therapy ; Intranasal ; Neurodegeneration ; Stroke Recovery
Language
english
Publication Year
2023
HGF-reported in Year
2023
ISSN (print) / ISBN
0027-8424
e-ISSN
1091-6490
Quellenangaben
Volume: 120,
Issue: 4,
Article Number: e2200057120
Publisher
National Academy of Sciences
Reviewing status
Peer reviewed
Institute(s)
Institute of Experimental Genetics (IEG)
POF-Topic(s)
30201 - Metabolic Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-500600-003
Scopus ID
85146408447
PubMed ID
36649432
Erfassungsdatum
2023-01-24