Trehalose (DB12310): A Comprehensive Monograph on a Bioprotectant Molecule from Excipient to Emerging Therapeutic

Executive Summary

Trehalose (DrugBank ID: DB12310) is a naturally occurring disaccharide that presents a compelling and paradoxical profile in the biopharmaceutical landscape. It is simultaneously a well-established, high-purity pharmaceutical excipient with an exceptional safety record and an investigational therapeutic agent with significant potential, particularly in neurodegenerative and ophthalmic diseases. This report provides a comprehensive analysis of Trehalose, synthesizing its physicochemical properties, complex pharmacology, clinical development status, safety profile, and global regulatory standing to provide a strategic perspective on its future.

The foundational characteristic of Trehalose is the exceptional stability of its α,α-1,1-glycosidic bond, which confers resistance to heat and acid hydrolysis. This property underpins its primary biological function as a bioprotectant, enabling organisms to survive extreme environmental stress, and makes it an ideal stabilizer for sensitive biologic drugs. As a therapeutic, Trehalose is being investigated for its potential to clear pathological protein aggregates implicated in neurodegenerative disorders such as spinocerebellar ataxia (SCA), amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and Parkinson's disease.

However, its therapeutic rationale is complicated by a central scientific controversy regarding its primary mechanism of action. While the prevailing hypothesis posits that Trehalose induces autophagy to clear cellular debris, a substantial body of evidence from in vitro studies suggests it may instead block autophagic flux. This mechanistic ambiguity represents a critical risk for its development in systemic diseases and points toward alternative or indirect mechanisms, such as modulation of the gut-brain axis.