Alzheimer's - Dementia, Author Interviews / 02.05.2017
Alzheimer’s Disease: Tramiprosate Envelopes Amyloid Protein To Prevent Misfolding Into Aggregates
MedicalResearch.com Interview with:
Dr. Petr Kocis PhD
Vice President Preclinical Development
Alzheon, Inc.
University of Oxford
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Researchers widely accept that amyloid plaques are the hallmark of Alzheimer’s disease. However, for many years, drug development has focused on the solid amyloid plaque as a primary disease culprit. Recent advances show that it is more likely that early stage soluble beta amyloid oligomers play a key role in the pathogenic process of Alzheimer’s disease.
A paper recently published by Alzheon, a company developing medicines for Alzheimer’s disease and other neurological disorders, suggests a new therapeutic mechanism for targeting toxic amyloid beta oligomers with a small molecule, tramiprosate, the active agent in the drug candidate, ALZ-801. ALZ-801 is a Phase 3-ready drug candidate that is an optimized prodrug of tramiprosate, with a substantially improved pharmacokinetic and safety profile compared to tramiprosate.
Alzheon scientists discovered that tramiprosate acts to inhibit the production of neurotoxic beta amyloid oligomers by ‘enveloping’ the amyloid peptide to prevent its misfolding into soluble amyloid aggregates. Beta amyloid oligomers are believed to be key drivers of the pathogenic process in Alzheimer’s disease (AD). This novel enveloping mechanism of tramiprosate prevents the self-assembly of misfolded proteins into beta amyloid oligomers that lead to amyloid aggregation and, subsequently, cause neuronal toxicity and clinical progression in Alzheimer’s disease. These results were published in the medical journal, CNS Drugs, and the paper is available through Open Access here. [“Elucidating the Aß42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer’s Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data”]
(more…)