The beta amyloid (β amyloid, Aβ) anti-aggregation mechanism of ALZ-801 in Alzheimer’s disease (AD) is mediated by its active molecule, tramiprosate. Tramiprosate binds directly to beta amyloid Aβ42 and Aβ40 peptides in the brain to inhibit the formation of toxic soluble oligomers that subsequently aggregate into beta amyloid fibrils and plaque. (Gervais et al. 2007; Martineau et al. 2010). Following cleavage from prodrug ALZ-801, tramiprosate is released in the body and penetrates into the brain where it directly interacts with soluble beta amyloid peptide monomers to block the pathological beta amyloid cascade. Blocking assembly of beta amyloid monomers prevents the formation of toxic beta amyloid oligomers. Tramiprosate has been found to maintain beta amyloid protein in a non-toxic, non-fibrillary, soluble form with an end result of inhibiting toxicity to brain cells.
In supportive, preclinical in vivo studies, tramiprosate treatment of TgCRND8 mice resulted in a significant reduction (∼30%) in brain beta amyloid plaque load (quantified via histopathology). Treatment with tramiprosate further significantly reduced both soluble and insoluble beta amyloid fractions (Gervais et al. 2007).
Long term oral therapy with ALZ-801 over time, is expected to prevent beta amyloid aggregation and inhibit the development of beta amyloid oligomeric pathology and resultant neurotoxicity, which is the hallmark of AD (Lacor et al. 2007; Demuro et al. 2010).