Findings Published Today in Journal of Neuroscience
AUSTIN, Texas, July 18, 2012 (GLOBE NEWSWIRE) -- Pain Therapeutics (Nasdaq:PTIE) today announced the publication of preclinical data that demonstrate a promising new approach to treat Alzheimer's disease.
Patients with Alzheimer's disease (AD) suffer from progressive and irreversible cognitive impairment that is widely believed to be caused by a protein called beta-amyloid. Scientists at City University of New York Medical School and Pain Therapeutics have now shown that a novel compound, PTI-125, can dramatically suppress the toxic effects of beta-amyloid. Results were demonstrated in a mouse model of AD, and remarkably, in brain tissue from deceased Alzheimer's patients. These novel findings suggest PTI-125 may improve cognition and protect against the toxic effect of beta-amyloid in neurons, raising hopes for a treatment to combat cognitive decline in AD. Today's publication also suggests the usefulness of this new approach to develop a noninvasive, blood-based biomarker and clinical diagnostic for AD.
The research is published today in The Journal of Neuroscience, the highest-ranking journal in its discipline. Data on this new approach were also recently presented at the 2012 Alzheimer's Association International Conference (AAIC), in Vancouver, Canada.
Pain Therapeutics owns worldwide commercial rights to PTI-125 and related technology.
Beta-amyloid is widely believed to be a primary causative agent in Alzheimer's disease. Existing therapeutic candidates mostly focus on clearing out beta-amyloid from the brain. In contrast, we demonstrate in today's publication a novel method to block the toxic effects of beta-amyloid by using a small molecule, which we designed, called PTI-125. PTI-125 binds with very high affinity to a novel target critical to beta-amyloid's toxicity. In doing so, PTI-125 disrupts beta-amyloid's toxic signals, expels existing beta-amyloid from alpha7-nicotinic acetylcholine receptors (α7nAChR) and reduces beta-amyloid-induced inflammation. PTI-125 is in the preclinical stage of drug development.
Abstract of Today's Publication
"Reducing Amyloid-Related Alzheimer's Disease Pathogenesis by a Small Molecule Targeting Filamin A"
Hoau-Yan Wang,1, 2 Kalindi Bakshi,1 Maya Frankfurt,3 Andres Stucky,1,2 Marissa Goberdhan,1,2 Sanket M. Shah1 and Lindsay H. Burns4
1Department of Physiology, Pharmacology and Neuroscience, City University of New York Medical School, New York, New York 10031, 2Department of Biology and Neuroscience, Graduate School of the City University of New York, New York, New York 10016, 3Department of Science Education, Hofstra North Shore–Long Island Jewish School of Medicine, Hempstead, New York 11549-1000, and 4Pain Therapeutics, Inc., Austin, Texas.
PTI-125 is a novel compound demonstrating a promising new approach to treating Alzheimer's disease (AD), characterized by neurodegeneration and amyloid plaque and neurofibrillary pathologies. We show that the toxic signaling of amyloid-β42 (Aβ42) by the α-nicotinic acetylcholine receptor (α7nAChR), which results in tau phosphorylation and formation of neurofibrillary tangles, requires the recruitment of the scaffolding protein filamin A (FLNA). By binding FLNA with high affinity, PTI-125 prevents Aβ42's toxic cascade, decreasing phospho-tau and Aβ aggregates and reducing the dysfunction of α7nAChRs, NMDARs, and insulin receptors. PTI-125 prevents Aβ42 signaling by drastically reducing its affinity for α7nAChRs and can even dissociate existing α7nAChR complexes. Additionally, PTI-125 prevents Aβ-induced inflammatory cytokine release by blocking FLNA recruitment to toll-like receptor 4, illustrating an anti-inflammatory effect. PTI-125's broad spectrum of beneficial effects is demonstrated here in an intracerebroventricular Aβ42 infusion mouse model of AD and in human postmortem AD brain tissue.
About Pain Therapeutics
Pain Therapeutics, Inc. is a biopharmaceutical company that develops novel drugs. The FDA has not approved any of our drug candidates for commercial sale. Our lead drug candidate, called REMOXY® (oxycodone) Extended-Release Capsules CII, is partnered with Pfizer, Inc. For more information, please visit www.paintrials.com.
Note Regarding Forward-Looking Statements: This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). Pain Therapeutics disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Safe Harbor for forward-looking statements contained in the Act. Examples of such statements include, but are not limited to, statements regarding the potential benefits of PTI-125 and its mechanism of action for treatment of AD and the potential for development of a noninvasive, blood-based biomarker and clinical diagnostic for AD as a result of findings from research related to PTI-125. Such statements are based on management's current expectations, but actual results may differ materially due to various factors. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in research, development, testing and pursuit of regulatory approval of PTI-125 or a biomarker and diagnostic for AD, unexpected adverse side effects or inadequate safety or therapeutic efficacy of PTI-125, inadequate efficacy of any biomarker or diagnostic developed from research related to PTI-125, the uncertainty of patent protection for our intellectual property or trade secrets, unanticipated additional research and development and other costs, and the potential for other competing products or therapies to be developed by competitors and potential competitors or others. For further information regarding these and other risks related to the Company's business, investors should consult the Company's filings with the Securities and Exchange Commission.
CONTACT: Peter S. Roddy
Vice President and Chief Financial Officer
Pain Therapeutics, Inc.