'Tau Is Not Cause Of Alzheimer's, It Is Effect' Note Experts At Anavex

Main Category: Alzheimer's / Dementia
Article Date: 06 Aug 2008 - 2:00 PDT

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On the heels of the widely publicized failure of anti-amyloid approaches to curing Alzheimer's, a lot of publicity has been given to another approach known as "Tau" (Neuro-Fibrillary Tangles or NFT) as a therapeutic target for Alzheimer's, as highlighted in last week's International Conference on Alzheimer's Disease in Chicago.

Experts at Anavex Life Sciences Corp. (AVXL.OB) (http://www.anavex.com) have provided clarification that Tau, like Amyloid-Beta, is an effect of Alzheimer's, not the cause. Oxidative Stress is the true cause of the disease. Both Amyloid-Beta and Tau, in fact, are preceded by Oxidative Stress and it is Oxidative Stress that is the cause of neuron degeneration.

Anavex is engaged in the development of drugs that protect neurons from Oxidative Stress. Anavex points out that this theory was endorsed by Rudy J. Castellani and his team in their article, Antioxidant protection and neurodegenerative disease: The role of amyloid-ß and tau (http://aja.sagepub.com/cgi/content/abstract/21/2/126). The paper notes that Tau (Neuro-Fibrillary Tangles of NFT) is formed after the oxidative stress is accumulated and outlines the evidence for this. In summary, Castellani says:

"Although both amyloid-B, and tau are essentially associated with etiology by various laboratories, the observed decrease in oxidative damage with amyloid-B and tau accumulation suggests, rather, a mechanism of survival. Moreover, as a consequence of age-related oxidative stress, there is an upregulation of phosphorylated tau and amyloid-B that result in NFT and senile plaques, respectively. Both lesions serve antioxidant functions and limit age-related neuronal dysfunction. However, in AD, this age-related oxidative stress is compounded by metabolic and metallic sources of oxidant stress that, despite greatly enhancing amyloid-B production and tau phosphorylation, lead to neurodegeneration and consequent dementia. In light of these observations, efforts aimed solely at eliminating amyloid-B appear short-sighted."

Anavex Life Sciences has developed an Alzheimer's drug candidate based on the theory that oxidative stress, not amyloid-beta plaques or Tau, is the cause of the disease. The drug protects neurons from the oxidative stress and addresses the very problem of the Alzheimer's disease. The company notes that preventing Tau predisposition without fighting the oxidative stress may lead researchers down a similar futile path that was followed with Amyloid-Beta as clinical trials demonstrated and Castellani theory states.

Promising Pre-clinical Studies

Anavex's alternative approach is showing great promise in early-stage testing. Anavex's drug candidate, known as ANAVEX 1-41, uses sigma receptors, a unique class of receptor molecules, to guard against oxidative stress and repair cells compromised by its effects. In advanced pre-clinical studies, ANAVEX 1-41 appeared to provide neurons with potent protection from oxidative stress. It also prevented amyloid beta from becoming toxic and causing any follow-on damage. Moreover, ANAVEX 1-41 reduced memory deficits in animal test subjects - a particularly notable finding, given the quest for a drug that can actively reverse the effects of the disease.

A program of further work is currently underway to further assess the compound, including ongoing pre-clinical studies being carried out in collaboration with the Université Montpellier in France. The company is moving forward aggressively with this work, which is designed to pave the way for a rapid move towards human testing, expected to commence in late 2008 or early 2009.

While much still needs to be done, Anavex is enormously pleased with its progress to date on this promising new approach to combating one of the world's most complex and devastating diseases.

About Anavex Life Sciences Corp.

Anavex Life Sciences Corp. is an emerging biopharmaceutical company engaged in the discovery and development of novel drug targets for the treatment of cancer and neurological diseases such as Alzheimer's, epilepsy and depression. The company's proprietary SIGMACEPTOR™ Discovery Platform involves the rational design of drug compounds that fulfil specific criteria based on unmet market needs and new scientific advances. Selected drug candidates demonstrate high, non-exclusive affinity for sigma receptors, which are involved in the modulation of multiple cellular biochemical signalling pathways.

ANAVEX's SIGMACEPTOR™-N program involves the development of novel and original drug candidates that target neurological and neurodegenerative diseases (Alzheimer's disease, epilepsy, depression, etc.) The company's lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for anti-amnesic, neuroprotective, anti-apoptotic, anti-oxidative, anti-inflammatory, anti-convulsive, anti-depressant and anxiolytic properties. The company believes that oxidative stress, not amyloid-beta, is the cause of Alzheimer's. ANAVEX 1-41, uses sigma receptors, a unique class of receptor molecules, to guard against oxidative stress and repair cells compromised by its effects. So far, through the advanced pre-clinical phase of development, the compound has performed extremely well in well-recognized animal models of Alzheimer's disease, underscoring the promise of this alternative approach to the disease.

ANAVEX SIGMACEPTOR™-C program involves the development of novel and original drug candidates targeting cancer. The company's lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for selective pro-apoptotic, anti-metastatic and low toxicity properties in various types of solid cancers such as melanoma, colon, prostate and. ANAVEX 7-1037 has already demonstrated its ability to significantly delay the growth of cancerous tumors in patient-derived xenografts during advanced pre-clinical studies.

http://www.anavex.com