Announcing a New Era in Alzheimer's

AsiaNet 51158

MONTE CARLO, Monaco, Oct. 31, 2012 /PRN=KYODO JBN/ --

     - The time for Tau is now as Phase 3 clinical trials get underway

      with a second-generation Tau Aggregation Inhibitor (TAI) aimed at

                    halting the progression of Alzheimer's

     TauRx Therapeutics Ltd announced today the initiation of two global Phase

3 clinical trials in mild to moderate Alzheimer's disease. These landmark

studies could provide the first definitive data on a Tau-based approach to

disease-modifying and preventative treatment of Alzheimer's for at least the

next 5-7 years, said Professor Claude Wischik, Chairman of TauRx and Professor

of Old Age Psychiatry at the University of Aberdeen, in a press conference at

the 5th Clinical Trials Conference on Alzheimer's Disease (CTAD) in Monte

Carlo, Monaco today.  

     The studies culminate three decades of research by Professor Wischik and

colleagues, including the original discovery of the Tau protein as the main

constituent of the Tangle pathology of Alzheimer's disease ['Tau tangles'], the

development of the first Tau Aggregation Inhibitor (TAI), and results from an

earlier Phase 2 clinical trial involving more than 300 patients that showed a

90% reduction in the rate of disease progression over two years.1

     "These Phase 3 studies are bringing us closer to finding an effective

treatment that can actually arrest the progression of the disease," said

Professor Wischik. "We are building on over thirty years of research, and the

encouraging results from our previous Phase 2 clinical trial in Alzheimer's

disease support an approach which targets the abnormal Tau aggregates in the

brain."

     The studies, which have already starting enrolling in the U.S., aim to

confirm the disease-modifying effects seen in the Phase 2 studies in mild to

moderate patients over an 18-month timeframe. The first study will involve 833

people with mild to moderate Alzheimer's disease over 12 months.2 The second

study will include 500 people with mild Alzheimer's disease over 18 months.3

     The study drug, LMTX(TM), is a second-generation TAI that targets the Tau

tangles and their precursors, dissolving them in order to halt their harmful

effects on memory.4-6 LMTX(TM) also works on the early stage Tau aggregates

(called 'ligomers') which are precursors to fully-formed tangles and are

thought to be particularly toxic.7

     "Clinicians devoted to Alzheimer's disease have been waiting for a

promising agent with disease-modifying properties," said Professor Serge

Gauthier of the McGill Centre for Studies in Aging, Quebec, Canada. "The basic

science data for this agent, particularly in the tauopathies, looks sound and

the interest among investigators and among families is high." Professor

Gauthier is a clinical investigator and scientific advisor for TauRx.

    The tangles in the brain were first reported by Dr. Alois Alzheimer in

1907,8 starting the century-long journey to understand the pathology leading to

their formation, their role in dementia, and, ultimately, how to stop their

spread through the brain.

     Professor Lon Schneider, MD, of the Keck School of Medicine at the

University of Southern California, a scientific advisor for TauRx, said:

"Successfully targeting Tau may be an important approach towards slowing and

ideally halting the neuro-degeneration that is characteristic of Alzheimer's

disease or frontotemporal dementia. Clinicians need these Phase 3 studies to

produce clear evidence that such an approach could lead to improved patient

outcomes."

     Countries in which the Phase 3 clinical trials will be conducted include

Australia, Belgium, Canada, Finland, France, Germany, Italy, Russia, Spain,

Netherlands, Singapore, Malaysia, Taiwan, U.S., and U.K.  Patients and

caregivers are invited to sign up for study updates at

www.AlzheimersStudies.com, as the clinical trials are initiated in the

countries selected.

     About Alzheimer's Disease and Tau Tangles:

     Alzheimer's disease is one of the most important health challenges

worldwide, and the most-common type of dementia. According to the Geneva-based

World Health Organization, global dementia cases are expected to double within

20 years to an estimated 65.7 million people [more than the entire population

of France currently at 63 million people].(9) In very early, asymptomatic

Alzheimer's, pre-tangle Tau aggregates (oligomers) and Tau protein tangles are

already present in the same regions of the brain where neuronal degeneration

and loss of neuronal cells eventually occur.(10,11) These changes first appear

20 - 30 years before the disease becomes clinically evident. With time, Tau

tangles spread from the entorhinal cortex (responsible for learning, memory,

thinking and planning) through the hippocampus to the neocortex (affecting the

ability to communicate, recognize family and loved ones and to care for

oneself), resulting in neuronal dysfunction and worsening of clinical

symptoms.(11) The spread is now thought to be due to a prion-like process

whereby the oligomers act as 'infectious particles' which are able to propagate

the abnormal aggregation of Tau protein from one neurone to the next.(12) These

oligomers recruit normal Tau to produce yet more infectious oligomers which

spread neuronal destruction throughout the brain.  

     About TauRx Therapeutics:

     TauRx Therapeutics Ltd was established in Singapore in 2002 with the aim

of developing new treatments and diagnostics for a range of neurodegenerative

diseases based on an entirely new approach which targets aggregates of abnormal

fibres of Tau protein that form inside nerve cells in the brain, giving rise to

Tangles. The TauRx team have since discovered that LMTX(TM)could also have

beneficial effects in several other neurodegenerative diseases associated with

Tau pathology, as well as other protein aggregation disorders including

Parkinson's, Huntington's and Frontotemporal Dementia [FTD-Pick's Disease],

Progressive Supranuclear Palsy and Cortico-Basal Degeneration. While TauRx

corporate headquarters are in Singapore, its primary research facilities are in

Aberdeen, Scotland.

For press enquiries please contact:

U.S. media contacts:

Liz Moench +1-610-659-5093

Courtney Hollinger +1-484-674 6800

Outside the U.S. media contacts:

Richard Anderson +44 (0)7973 950376

Email: press@taurx.com

References:

1. Wischik CM, Bentham P, Wischik DJ, Seng KM. Tau aggregation inhibitor (TAI)

therapy with remberTM arrests disease progression in mild and moderate

Alzheimer's disease over 50 weeks. Alzheimer's and Dementia 2008;4:T167.

Abstract available at:

http://www.alzheimersanddementia.com/article/S1552-5260(08)00598-0/fulltext.

Accessed October 2012.

2. ClinicalTrials.gov. Safety and efficacy study evaluating TRx0237 in subjects

with mild to moderate Alzheimer's disease. Available at:

http://www.clinicaltrials.gov/ct2/show/NCT01689246. Accessed October 2012.

3. ClinicalTrials.gov. Safety and efficacy study evaluating TRx0237 in subjects

with mild Alzheimer's disease. Available at:

http://www.clinicaltrials.gov/ct2/show/NCT01689233. Accessed October 2012.

4. Wischik CM, Edwards PC, Lai RYK, Roth M, Harrington CR. Selective inhibition

of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci

USA 1996;93:11213-11218. Full article available at:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC38310/. Accessed October 2012.

5. Wischik CM, Lai RYK, Harrington CR. Modelling prion-like processing of tau

protein in Alzheimer's disease for pharmaceutical development. In: Brain

Microtubule Associated Proteins: Modifications in Disease, eds. Avila J, Brandt

R, Kosik KS. (1997) pp. 185-241. Amsterdam: Harwood Academic Publishers.

6. Wischik CM, Wischik DJ, Storey JMD, Harrington CR. Rationale for

tau-aggregation inhibitor therapy in Alzheimer's disease and other tauopathies.

In: Emerging Drugs and Targets for Alzheimer's Disease. Volume 1: Beta-Amyloid,

Tau Protein and Glucose Metabolism, ed. Martinez A. (2010) pp. 210-232.

Cambridge: RSC Publishing.

7. Taniguchi S, Suzuki N, Masuda M, Hisanaga S, Iwatsubo T, Goedert M, et al.

Inhibition of heparin-induced tau filament formation by phenothiazines,

polyphenols, and porphyrins. J Biol Chem 2005;280:7614-7623. Full article

available at: http://www.jbc.org/content/280/9/7614.long. Accessed October 2012.

8. Alzheimer A. On a peculiar disease of the cerebral cortex. Allgemeine

Zeitschrift fu;r Psychiatrie und Psychisch-Geritlich Medicin 1907;64:146-148.

9. World Health Organization News Release. Dementia cases set to triple by 2050

but still largely ignored. Available at:

http://www.who.int/mediacentre/news/releases/2012/dementia_20120411/en/index.html.

Accessed October 2012.

10. Mukaetova-Ladinska EB, Garcia-Sierra F, Hurt J, Gertz HJ, Xuereb JH, Hills

R, et al. Staging of cytoskeletal and beta-amyloid changes in human isocortex

reveals biphasic synaptic protein response during progression of Alzheimer's

disease. Am J Pathol 2000;157:623-636. Full article available at:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850134/. Accessed October 2012.

11. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes.

Acta Neuropathol 1991;82:239-259. Abstract available at:

http://www.ncbi.nlm.nih.gov/pubmed/1759558. Accessed October 2012.

12. Soto C. Transmissible proteins: expanding the prion heresy. Cell 2012;

149:968-977. Full article available at:

http://www.sciencedirect.com/science/article/pii/S0092867412005818. Accessed

October 2012.

     SOURCE: TauRx Therapeutics Ltd