Treatment of Alzheimer's Disease with Benfotiamine and its Derivatives

Background & Unmet Need

• Alzheimer’s disease (AD) treatments which target amyloid-β are often ineffective, suggesting the need for novel therapeutics
• Other biomarkers of AD include inflammation, oxidative stress, and metabolic dysregulation
• Reduction of cerebral glucose metabolism correlates highly with cognitive decline
• Thiamine-dependent enzymes regulate cerebral glucose metabolism, and the decline of their activity is apparent in AD patients
• Advanced glycation end products (AGE) are toxic protein modifications indicative of abnormal glucose metabolism
• Unmet Need: Development of an AD therapeutic targeting glucose metabolism abnormalities

Technology Overview

• The Technology: Method to treat AD by administering benfotiamine (BFT) or its derivatives
• BFT is a synthetic thiamine precursor which raises blood thiamine levels, and was shown in a Phase 2a trial to improve patient outcomes based on multiple clinical and biological markers of AD
• BFT or a placebo was administered orally for 12 months to patients with mild cognitive impairment (MCI) or mild AD
• Mean blood thiamine levels increased 120-fold higher in treatment group than placebo
• PoC Data: The increase in ADAS-Cog was 43% lower in the treatment group, indicating less cognitive decline (p = 0.125)
• Clinical dementia rating was 77% lower in treatment group (p = 0.034)
• Increase in AGE was significantly reduced in treatment group (p = 0.044)

Technology Applications

• Therapeutic for the treatment and prevention of AD
• Elucidation of AD biomarkers to reveal additional therapeutic targets
• Benfotiamine provides a starting point for medicinal chemistry efforts to identify improved molecules
• Therapeutic for other diseases with tau pathology, such as frontotemporal dementia and progressive supranuclear palsy

Technology Advantages

• Non-amyloid-β target, which historically show low efficacy
• Cerebral glucose metabolism often changes decades before AD is diagnosed, allowing for early intervention of BFT treatment
• Oral benfotiamine is safe and already available as an OTC supplement