Dataset Information

Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets.

ABSTRACT: 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.

SUBMITTER: Correa D

PROVIDER: S-EPMC9942809 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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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.

Correa Daphne D Scheuber Myriam I MI Shan Huimin H Weinmann Oliver W OW Baumgartner Yves A YA Harten Aliona A Wahl Anna-Sophia AS Skaar Kirstin L KL Schwab Martin E ME

Proceedings of the National Academy of Sciences of the United States of America 20230117 4

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 intra ...[more]

PMID: 36649432

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Project description:Background: The management of various central nervous system (CNS) disorders has been challenging, due to highly compact blood-brain barrier (BBB) impedes the access of most pharmacological agents to the brain. Among multiple strategies proposed to circumvent this challenge, intranasal delivery route has sparked great interest for brain targeting in the past decades. The aim of this study was to apply scientometric method to estimate the current status and future trends of the field from a holistic perspective. Methods: All relevant publications during 1998-2020 were retrieved from the Web of Science Core Collection (SCIE, 1998-present). Two different scientometric software including VOS viewer and CiteSpace, and one online platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of journals, countries, institutes, authors, references and keywords. Results: A total of 2,928 documents, including 2,456 original articles and 472 reviews, were retrieved. Our analysis revealed a significant increasing trend in the total number of scientific publications over the past 2 decades (R 2 = 0.98). The United States dominated the field, reflecting in the largest amount of publications (971), the highest H-index (99), and extensive international collaboration. Jamia Hamdard contributed to most publications. Frey WH and Illum L were key researchers with the highest number of publications and citations, respectively. The International Journal of Pharmaceutics was the most influential academic journal, and Pharmacology/Pharmacy and Neurosciences/Neurology were the hottest research categories in this field. Based on keywords occurrence analysis, four main topics were identified, and the current research focus of this field has shifted from cluster 4 (pathways and mechanisms of intranasal delivery) to cluster 2 (the study of nasal drug delivery systems), especially the nanostructured and nano-sized carrier systems. Keywords burst detection revealed that the research focus on oxidative stress, drug delivery, neuroinflammation, nanostructured lipid carrier, and formulation deserves our continued attention. Conclusion: To the authors' knowledge, this is the first scientometric analysis regarding intranasal delivery research. This study has demonstrated a comprehensive knowledge map, development landscape and future directions of intranasal delivery research, which provides a practical and valuable reference for scholars and policymakers in this field.

Dataset Information

Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets.

Publications

Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets.

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