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Mechanistic Model of Alzheimer's Disease Endorsing PBT2
Posted: Monday, March 26, 2012 4:17 PM
Joined: 12/6/2011
Posts: 3326

From Alzheimer's Daily News:

(Source: MarketWatch) - An article in the journal PLoS ONE endorses PBT2's potential to treat Alzheimer's disease. The paper, entitled "The Zinc Dyshomeostasis Hypothesis of Alzheimer's Disease", presents an integrated explanation of the major pathological features of Alzheimer's disease, based upon a combination of new experimental data and mathematical modeling.

Rudy Tanzi, Professor of Neurology at Harvard University and Prana's Chief Scientific Advisor, explained that "the hallmark pathological features of Alzheimer's disease are the amyloid plaques, composed of the Abeta protein, and neurofibrilliary tangles (NFTs), composed of Tau protein. Everything we have learned from the genetics of Alzheimer's Disease indicates that the disease is caused by excessive accumulation of the Abeta protein in the brain. We also know that hyperphosphorylation of the Tau protein which forms NFTs is the feature of the disease which correlates with neuronal damage and cognitive loss. Prana's drug PBT2 reduces levels of both Abeta and hyperphosphorylated tau in animal studies and improved cognition and lowered Abeta in a Phase 2a clinical trial of Alzheimer's disease patients.

"So, Alzheimer's disease can be defined as an amyloid-induced tauopathy. The big question is this - how does amyloid aggregation lead to NFTs? In this paper we propose that at least part of the answer to that question is zinc dyshomeostasis, that is to say, abnormal distribution of zinc in the brains of Alzheimer's disease sufferers. The drug PBT2 directly addresses this problem by binding zinc and normalizing its distribution. This bodes very well for the current PBT2 clinical trial that is in progress," concluded Dr. Tanzi.

The paper builds on previous findings that as we age our ability to maintain normal zinc distribution deteriorates. Abeta forms amyloid by capturing and holding zinc, which in turn further reduces our ability to maintain normal zinc distribution. "This is a vicious pathological cycle. PBT2 interrupts this cycle, re-distributing zinc needed for healthy brain function," commented Prana's Head of Research, Robert Cherny.

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