Effects of intranasal antibodies on murine models of neurological disorders: A systematic review.

Neurological disorders significantly impact billions of individuals worldwide, representing a leading cause of disability and premature death. Antibody-based therapeutics, known for their high target specificity, have been investigated for various neurological disorders, including Alzheimer's and Parkinson's diseases. However, despite advancements in neuropharmacology, the use of therapeutic antibodies in neurological disorders faces considerable challenges, particularly due to their limited bioavailability across the blood-brain barrier and often invasive administration protocols. In this context, the intranasal route has emerged as a promising noninvasive alternative for drug delivery, prompting direct brain access and rapid therapeutic effects, especially for larger molecules such as antibodies. Therefore, we aimed at the present study to gather information on the current state of research in the field and to summarize potential trends in methodology employed in such studies. The present systematic review identified a total of 1135 articles through databases such as Scopus, Web of Science, and PubMed, ultimately including 31 articles for detailed analysis. The study methodology was preregistered at Open Science Framework platform. Our findings indicate that Alzheimer's disease is the most studied condition, and the hippocampus is the most frequently evaluated brain area. Monoclonal antibodies were the predominant therapeutic agents utilized, and significant variation in dosages used were noted. Furthermore, despite being high-molecular entities, antibodies can target both intracellular and extracellular proteins and eventually bring neuroprotective effects after intranasal administration. In summary, while this systematic review highlights the potential of intranasal antibodies for treating neurodegenerative diseases, there is significant room for additional studies on their mechanisms of action, long-term effects, and strategies to clinical translation.