Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis.

Amyloid β-peptide (Aβ) is a major constituent of senile plaques in Alzheimer's disease (AD). Neurotoxicity results from the conformational transition of Aβ from random-coil to β-sheet and its oligomerization. Among a series of ionic compounds able to interact with soluble Aβ, Tramiprosate (3-amino-1-propanesulfonic acid; 3APS; Alzhemed™) was found to maintain Aβ in a non-fibrillar form, to decrease Aβ42-induced cell death in neuronal cell cultures, and to inhibit amyloid deposition. Tramiprosate crosses the murine blood-brain barrier (BBB) to exert its activity. Treatment of TgCRND8 mice with Tramiprosate resulted in significant reduction (∼30%) in the brain amyloid plaque load and a significant decrease in the cerebral levels of soluble and insoluble Aβ40 and Aβ42 (∼20–30%). A dose-dependent reduction (up to 60%) of plasma Aβ levels was also observed, suggesting that Tramiprosate influences the central pool of Aβ, changing either its efflux or its metabolism in the brain. We propose that Tramiprosate, which targets soluble Aβ, represents a new and promising therapeutic class of drugs for the treatment of AD.