Allon announces davunetide improves motor function and brain pathology in a Parkinson?s disease model

VANCOUVER, B.C. — Allon Therapeutics Inc. (TSX: NPC) announced today that a research project funded by the Michael J. Fox Foundation (MJFF) for Parkinson’s Research found that intranasal davunetide treatment significantly improved motor function and brain pathology in a mouse model which replicates certain characteristics of Parkinson’s disease (PD), a progressive neurodegenerative disease. Treatment with davunetide caused a 38% improvement in motor performance and coordination relative to controls.

 

An estimated 1.5 million people in North America suffer from PD and its incidence is expected to increase significantly over the next 25 years as the population ages. While there are therapies available to help patients manage many of the symptoms, there are currently no known treatments to stop the progression of PD.

 

The study results were published this month in the online edition of the international peer-reviewed journal Molecular and Cellular Neuroscience under the title: “A pilot trial of the microtubule-interacting peptide (NAP) in mice overexpressing alpha-synuclein shows improvement in motor function and reduction of alpha-synuclein inclusions.”

 

The mice were bred to have an abnormal accumulation of the protein α-synuclein, which is associated with several neurodegenerative disorders (synucleinopathies), including sporadic PD. Most animal models of PD can identify symptomatic treatments. The α-synuclein mouse model progressively develops pathology which leads to functional impairment and is useful to identify potential disease-modifying therapeutics.

 

Bruce Morimoto, Allon’s Vice President of Drug Development and the principal investigator for the research project said davunetide was chosen for this research in Parkinson’s disease because of its broad neuroprotective properties demonstrated previously in numerous models of neurodegeneration. “Davunetide can improve behavioral outcomes through a mechanism involving microtubules,” Morimoto said.

 

In the study, performed by the laboratory of Prof. Marie-Françoise Chesselet of the University of California, Los Angeles (UCLA), the Charles H. Markham Professor of Neurology and Chair of the Department of Neurobiology, α-synuclein mice were treated with davunetide daily for two months. At the end of the treatment period, these mice and various control groups were tested for motor function, coordination and activity. The davunetide treated α-synuclein mice showed a 38% decrease in the number of errors per step in the beam traversal test, a measure of motor function.

 

The brain pathology was examined for physical evidence of α-synuclein accumulation and inclusions. Davunetide treatment resulted in a reduction in α-synuclein inclusions in the substantia nigra brain region. “The substantia nigra controls motor activity, so the behavioural improvement in motor function correlates well with the reduction of α-synuclein pathology in that region,” said Dr. Morimoto.

 

“We are delighted to see the effect of davunetide in these experiments" Prof. Chesselet said. "These promising results show that davunetide should be further investigated as a potential treatment for Parkinson’s.”

 

Allon announced November 30, 2010 that the MJFF for Parkinson’s Research, encouraged by these preclinical results, provided an additional $625,000 of research funding to the Company’s davunetide research in PD. The decision to provide additional funding is also driven by the advanced clinical status of davunetide that could allow rapid development in Parkinson’s disease. Using the same model, this newly funded research will assess whether different doses and/or longer treatment duration results in a more robust impact on brain pathology and motor function.

 

Molecular and Cellular Neuroscience publishes original research considered by the editors to have exceptional significance for the field. The journal is published by Elsevier, a world-leading publisher of scientific, technical and medical information products and services.

 

About the Michael J. Fox Foundation for Parkinson's Research

MJFF is dedicated to finding a cure for Parkinson’s disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson’s today. The Foundation has funded more than $224 million in research to date. For additional information please visit: www.michaeljfox.org.

 

About davunetide

Davunetide is derived from a naturally occurring neuroprotective brain protein known as activity dependent neuroprotective protein (ADNP). Allon’s laboratory and animal studies have shown that davunetide improves cognition in a number of disease models through a mechanism believed to involve effects on microtubules, structures in the brain critical to communication between cells.

 

Allon is currently enrolling patients in a pivotal Phase 2/3 clinical trial evaluating davunetide as a potential treatment for progressive supranuclear palsy (PSP), a rapidly-progressing and fatal degenerative brain disease which is often misdiagnosed as Parkinson’s or Alzheimer’s disease.

 

About Allon’s neuroprotective platforms

Allon’s two neuroprotective technology platforms are based on two naturally occurring proteins produced by the brain in response to a range of insults. The platforms are activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF).

 

Because the two platforms are based on different proteins, the drugs from each are different molecules with different therapeutic mechanisms and distinct commercial opportunities. Clinical-stage drugs based on davunetide are derived from ADNP, while preclinical stage drug AL-309 is derived from ADNF. Davunetide is focused on Alzheimer’s disease, cognitive impairment associated with schizophrenia, and progressive supranuclear palsy (PSP). AL-309 is being developed for the treatment of peripheral neuropathies and is administered orally or subcutaneously.

 

About Allon

Allon Therapeutics Inc. is a clinical-stage biotechnology company focused on developing the first drugs that impact the progression of neurodegenerative diseases. Allon’s lead drug davunetide, is proceeding in a Phase 2/3 clinical trial in an orphan indication, progressive supranuclear palsy (PSP), under an SPA with the FDA. This pivotal trial is based upon statistically significant human efficacy demonstrated in amnestic mild cognitive impairment, cognitive impairment associated with schizophrenia, and positive biomarker data. The Company is listed on the Toronto Stock Exchange under the trading symbol “NPC” (Neuro Protection Company™) and based in Vancouver. For additional information please visit the Company's website: www.allontherapeutics.com.

 

Forward Looking Statements

Statements contained herein, other than those which are strictly statements of historical fact may include forward-looking information. Such statements will typically contain words such as "believes", "may", "plans", "will", "estimate", "continue", "anticipates", "intends", "expects", and similar expressions. While forward-looking statements represent management’s outlook based on assumptions that management believes are reasonable, forward-looking statements by their nature are subject to known and unknown risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from any future results, events or developments expressed or implied by them. Such factors include, among others, the inherent uncertainty involved in scientific research and drug development, Allon's early stage of development, lack of product revenues, its additional capital requirements, the risks associated with successful completion of clinical trials and the long lead-times and high costs associated with obtaining regulatory approval to market any product which Allon may eventually develop. Other risk factors include the limited protections afforded by intellectual property rights, rapid technology and product obsolescence in a highly competitive environment and Allon’s dependence on collaborative partners and contract research organizations. These factors can be reviewed in Allon’s public filings at www.sedar.com and should be considered carefully. Readers are cautioned not to place undue reliance on such forward-looking statements.

 

Posted: February 2011

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