Summary
PHASE II RANDOMIZED CONTROLLED TRIAL OF BENFOTIAMINE IN EARLY ALZHEIMER'S DISEASE - WE PROPOSE A SEAMLESS PHASE 2A-2B TRIAL INVESTIGATING BENFOTIAMINE, A PRODRUG OF THIAMINE, AS A FIRST-IN- CLASS SMALL MOLECULE TREATMENT FOR EARLY ALZHEIMER'S DISEASE (AD). WE CALL THIS PROPOSED TRIAL `BENFOTIAMINE IN EARLY ALZHEIMER'S DISEASE (BEAD)”. BRAIN TISSUE THIAMINE DEFICIENCY CAUSES MEMORY DEFICITS THAT ARE REVERSIBLE WITH THIAMINE TREATMENT IN PRECLINICAL AD MODELS AND IN HUMAN CONDITIONS INCLUDING WERNICKE KORSAKOFF SYNDROME. IN ANIMAL MODELS OF MILD IMPAIRMENT OF OXIDATIVE METABOLISM (I.E., THIAMINE DEFICIENCY), NEURONAL LOSS IS ACCOMPANIED BY CHANGES IN NEUROFILAMENT LIGHT (NFL), BY INCREASED NEUROINFLAMMATION (GLIAL FIBRILLARY ACID PROTEIN GFAP), BY ELEVATION OF ADVANCED GLYCATION END PRODUCTS (AGE) AND BY INCREASED PLAQUE AND BY TANGLE PATHOLOGY, ALL OF WHICH OCCUR IN AD. BENFOTIAMINE DRAMATICALLY RAISES BLOOD AND BRAIN TISSUE THIAMINE IN THESE MODELS, CONFERRING BEHAVIORAL BENEFIT AND RE
