Can Salivary Exosomes Derived from High-Brain Coherence States Restore Bioelectric Homeostasis and Ameliorate TDP-43 Proteinopathy in ALS/FTD Organoid Models ? A Theoretical Pilot Protocol and Hypothesis . Project : TroJex - Mini

ABSTRACT Background: Sporadic Amyotrophic Lateral Sclerosis (sALS) and Frontotemporal Dementia depolarization and disruption of transmembrane potential as a potential upstream pathogenic (FTD) converge on TDP-43 proteinopathy. Emerging evidence implicates bioelectric mechanism, operating independently of genetic mutations. Hypothesis: We hypothesize that salivary exosomes secreted during High Brain Coherence States (HBCS) possess a restorative bioelectric signature. Administration of HBCS-derived salivary exosomes will induce restoration of resting membrane potential via neuronal repolarization and mitigate TDP-43 mislocalization. The predicted downstream outcome is rescue of bioenergetic capacity in ALS motor neurons and re-establishment of neuronal networks in FTD. Pilot Observation: A single subject completed n=48 trials of an intention-modulated synchronization task over 14 days. Mean hit rate was 33% vs 16.67% chance, correlating with self-reported Brain Coherence State (BCS). Proposed Methodology: Salivary exosomes will be isolated from donor saliva collected during verified HBCS and applied to human iPSC-derived 3D ALS/FTD organoids. Outcomes: patch-clamp Vmem and quantitative cytoplasmic TDP-43. Conclusion: This proposes a novel therapeutic paradigm: intercellular transfer of bioelectric state via non-invasive, salivary-derived exosomes to correct membrane potential dysfunction and proteinopathy in TDP-43 diseases. Keywords: ALS, FTD, TDP-43, Bioelectricity, Salivary Exosomes, Membrane Potential, Neuronal Repolarization, Brain Coherence, NeuroScience