Development of a therapeutic nanobody targeting brain TNFa for the treatment of Alzheimer Disease

Abstract: This project seeks to advance the development of humanized TNFα inhibitors (INNs) as a novel therapeutic approach for Alzheimer's disease (AD). Our innovative INNs are designed to effectively inhibit TNFα while crossing the blood-brain barrier, targeting the neuroinflammatory processes central to AD pathology. Building on Phase I achievements, which included identifying INNs with high TNFα inhibitory activity and favorable blood-brain barrier permeability, Phase II will focus on rigorous preclinical evaluations in human-induced neurons, App- humanized rats, and familial and late-onset AD rat models. We will optimize INN formulations, characterize pharmacologic and toxicologic parameters, assess their immunogenicity, and begin establishing manufacturing processes for IND filing and clinical development. The success of this project could lead to a transformative treatment for AD, addressing a critical unmet need in neurodegenerative disease management.