Therapy Areas: Central Nervous System
Alzheon Scientists Discover Endogenous Substance in Human Brain That Inhibits Formation of Toxic Beta Amyloid Oligomers, Key Driver of Alzheimer's Disease
8 August 2018 - - An endogenous substance has been discovered in human brain that inhibits the formation of neurotoxic beta amyloid oligomers, which are key drivers of AD pathogenesis, US-based biopharmaceutical company Alzheon, Inc. said.

The substance was identified as 3-sulfopropanoic acid (3-SPA), the primary metabolite of tramiprosate and of its prodrug ALZ-801 in humans.

The cognitive improvements observed in AD patients in the tramiprosate Phase 3 studies may be attributed, in part, to the therapeutic effects of 3-SPA in the brain.

According to the company, this discovery indicates a potential protective role of 3-SPA in aging human brains and in AD, and elucidates the beneficial pharmaceutical attributes of ALZ-801, including a favorable safety profile, selectivity against Aβ oligomers, and excellent brain penetration.

In this new study, Alzheon scientists expanded on the previous finding that tramiprosate and its prodrug ALZ-801 are consistently metabolized in humans to a single major metabolite, 3-SPA.

The new analyses found that 3-SPA inhibits the formation of toxic soluble Aβ oligomers, comparable to the recently described effects of tramiprosate.

In evaluations of non-treated and treated AD patients, Alzheon scientists showed that the levels of 3-SPA were up to 12 times greater in AD patients who received oral tramiprosate, than in drug-naïve or placebo-treated patients.

These data further elucidate the mechanism of action supporting the development of Alzheon's Phase 3-ready candidate ALZ-801, an optimized prodrug of tramiprosate, with a substantially improved pharmacokinetic and safety/tolerability profile compared to tramiprosate.

The presence of an endogenous substance that can prevent Aβ oligomer formation also suggests the possibility of a protective endogenous anti-Aβ oligomer pathway within the human central nervous system, with the potential to prevent or delay the onset of AD. Such physiological anti-Aβ oligomer pathway could modulate the neurotoxic effects of abnormal Aβ aggregation in the aging human brain.

The study entitled "Discovery and Identification of An Endogenous Metabolite of Tramiprosate and its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in Human Brain," appeared in the most recent issue of the peer-reviewed publication CNS Drugs.
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