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.
GC Biopharma's GC1130A receives EMA Orphan Drug Designation
Guangzhou Fermion Technology's FZ008-145 IND application receives Chinese regulatory approval
Newron enrols 290 patients in schizophrenia study
Vistagen granted European patent for AV-101 to treat neuropathic pain
Alora Pharmaceuticals announces Relexxii commercial launch
IGC Pharma granted patent for Alzheimer's drug formulation
NRx Pharmaceuticals signs data agreement with Columbia University for IV Ketamine trials
Cambridge Cognition launches AQUA for automated quality assurance in CNS clinical trials
Shanghai Zhimeng Biopharma's CB03 receives US FDA orphan drug designation
Genentech's Alecensa demonstrates 76% reduction in disease recurrence risk
NRx Pharmaceuticals announces presentation at 8th Annual Dawson James Conference