Welcome!

News Feed Item

Addex Dipraglurant Reduces Motor Abnormalities in a Preclinical Model Relevant for Several Rare types of Dystonia

GENEVA -- (Marketwire) -- 01/29/13 -- Addex Therapeutics / Addex Dipraglurant Reduces Motor Abnormalities in a Preclinical Model Relevant for Several Rare types of Dystonia.

Processed and transmitted by Thomson Reuters ONE.

The issuer is solely responsible for the content of this announcement.

Dipraglurant, a novel oral small molecule negative allosteric modulator of mGlu5 receptor, on track for Phase 2 clinical testing in the second half of 2013

Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced positive preclinical data for its mGlu5 negative allosteric modulator (NAM) oral small molecule, dipraglurant, in a validated rodent model of dystonia, a spectrum of disorders, that includes several rare diseases and is characterized by debilitating involuntary muscle contractions and body movements. This is an area of high unmet medical need where many patients are left inadequately treated with the current standard of care. Dipraglurant demonstrated a robust and dose-dependent reduction in severity of a dystonia-like attack, induced by caffeine in the tottering mouse model. These data are consistent with earlier reported Addex findings in a Phase 2a clinical trial measuring levodopa-induced dyskinesia in Parkinson's patients as well as a non-human primate model of Parkinson's-related dystonia.

"The effects of dipraglurant in the mouse model are very compelling. They provide additional support for further exploration of mGlu5 inhibitors as a novel treatment for dystonia and also open new therapeutic avenues" said Professor Ellen Hess at Emory University (USA) in whose laboratory the study was performed.

The validation of the tottering mouse model in the laboratory of Professor Hess has been funded in part by the Bachmann-Strauss Dystonia and Parkinson Foundation. The model recapitulates key genetic and phenotypic features of so called episodic neurological disorders, that involve aberrant calcium channel functioning and susceptibility to neurological attacks in response to stress, alcohol or caffeine. In the study, acute, oral administration of dipraglurant (10, 30, 50 mg/kg) resulted in dose-dependent reductions of dystonia scores, achieving significant reductions at the highest dose in comparison to vehicle treatment. In a sub-group of experimental animals, dipraglurant fully blocked the onset of dystonia. These results demonstrate the potential of mGlu5 inhibition as a novel approach for the treatment of multiple types of dystonias, as well as other rare neurological conditions including familial hemiplegic migraine type 1, episodic ataxia type 2, and periodic paralysis.

"We are pleased that we continue to see broad therapeutic application for dipraglurant," said Bharatt Chowrira, CEO at Addex. "As we continue to seek a partner to advance dipraglurant in Parkinson's levodopa-induced-dyskinesia, we see great opportunity to take the compound forward in several rare disease indications including certain forms of dystonias. We look forward to starting Phase 2 clinical testing in the second half of 2013 with this potentially important movement disorder therapeutic".

About Dipraglurant

Dipraglurant is an oral, small molecule allosteric modulator that inhibits selectively the metabotropic glutamate receptor 5 (mGlu5), a Class C G-Protein Coupled Receptor (GPCR), with potential to be used in combination with levodopa or dopamine agonists or as a standalone treatment for Parkinson's disease levodopa-induced dyskinesia (PD-LID), motor and non-motor symptoms of Parkinson's disease and other movement disorders. Data from a recent Phase 2a show that dipraglurant met the primary objective of the study by exhibiting a good safety and tolerability profile. Dipraglurant also demonstrated a statistically significant reduction in LID severity with both 50 and 100 mg doses. Dipraglurant appears to reduce dystonia severity in addition to chorea, the two major LID components. In a double-blind, placebo-controlled study conducted in the US and Europe, the primary objective was to demonstrate safety and tolerability in PD-LID patients. In addition, the trial was designed to evaluate exploratory efficacy as a secondary objective. Efficacy was measured using the modified Abnormal Involuntary Movement Scale (mAIMS), patient diaries documenting "off-time" (impaired voluntary movement), "on-time" (with or without dyskinesia) and sleep. Additional endpoints include the Unified Parkinson's Disease Rating Scale (UPDRS), the Clinician & Patient Global Impression of Change (CGIC & PGIC), and an evaluation of the patients' mood using the Hospital Anxiety & Depression Score. The trial was supported by a grant from The Michael J. Fox Foundation for Parkinson's Research.

mGlu5 Inhibition

There is increasingly convincing evidence that mGlu5 inhibition may be a valuable new strategy for treating a number of important diseases and conditions, such as Parkinson's disease, Parkinson's disease levodopa-induced dyskinesia (PD-LID), anxiety, depression, pain, tardive dyskinesia, dystonia, addiction, autism and Fragile X syndrome. With regards to Parkinson's disease, recent clinical and preclinical evidence suggest that mGlu5 inhibition may have an effect on parkinsonian motor symptoms as well as dyskinesia. MGlu5 is found in regions of the brain considered to be key control points in the neuronal movement circuits affected by abnormal signaling by the neurotransmitter glutamate in Parkinson's disease. Perturbations in glutamate signaling (along with disruptions in dopaminergic signaling) are believed to be an underlying cause of movement disorders like Parkinson's disease. As such, inhibiting mGlu5 could act to re-establish normal movement via a non-dopaminergic mechanism. Separately, preclinical findings also suggest that mGlu5 inhibitors may be neuroprotective and may, therefore, hold potential as disease modifying agents that can slow or prevent progression of Parkinson's disease.

About Dystonia

Dystonia is a movement disorder that causes the muscles to contract and spasm involuntarily, according to the Dystonia Medical Research Foundation. The involuntary muscle contractions force the body into repetitive and often twisting movements as well as awkward, irregular postures. There are approximately 13 forms of dystonia, and dozens of diseases and conditions include dystonia as a major symptom. Dystonia may affect a single body area or be generalized throughout multiple muscle groups. Dystonia affects men, women, and children of all ages and backgrounds. Estimates suggest that no less than 300,000 people in North America are affected. Dystonia causes varying degrees of disability and pain, from mild to severe. There is presently no cure, and, although many drugs are utilized to try to treat dystonia, the leading treatment is botox injections and many patients are left with inadequate efficacy. Dipraglurant has been shown to effectively reduce dystonia in both a clinical study and preclinical models of Parkinson's disease levodopa-induced dyskinesia (PD-LID). The neurophysiology of different forms of dystonia is thought to be similar and recent preclinical data in dystonia - suggesting that dipraglurant may also work for non-parkinsonian forms of dystonia.

Addex Therapeutics (www.addextherapeutics.com) discovers and develops an emerging class of small molecule drugs, called allosteric modulators, which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. The Company uses its proprietary discovery platform to address receptors and other proteins that are recognized as attractive targets for modulation of important diseases with unmet medical needs. The Company's two lead products are being investigated in Phase 2 clinical testing: dipraglurant (ADX48621, an mGlu5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-LID) and dystonia; and ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals Inc. to treat schizophrenia and anxiety seen in patients suffering from major depressive disorder. Addex also is advancing several preclinical programs including: GABA-BR positive allosteric modulator (PAM) for Charcot-Marie-Tooth (type 1a) disease, spasticity in patients with multiple sclerosis (MS), pain, overactive bladder and other disorders; mGlu4 PAM for MS, Parkinson's disease, anxiety and other diseases. In addition, Addex is applying its proprietary discovery platform to identify highly selective and potent allosteric modulators of a number of both GPCR and non-GPCR targets that are implicated in diseases of significant unmet medical need.

Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Therapeutics, formerly known as, Addex Pharmaceuticals, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Therapeutics regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutics targets will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Therapeutics is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.

This announcement is distributed by Thomson Reuters on behalf of Thomson Reuters clients. The owner of this announcement warrants that:

(i) the releases contained herein are protected by copyright and other applicable laws; and

(ii) they are solely responsible for the content, accuracy and originality of the information contained therein.

Source: Addex Therapeutics via Thomson Reuters ONE

[HUG#1673755]

Tim Dyer
Chief Financial Officer
Addex Therapeutics
+41 22 884 15 61
Email Contact

More Stories By Marketwired .

Copyright © 2009 Marketwired. All rights reserved. All the news releases provided by Marketwired are copyrighted. Any forms of copying other than an individual user's personal reference without express written permission is prohibited. Further distribution of these materials is strictly forbidden, including but not limited to, posting, emailing, faxing, archiving in a public database, redistributing via a computer network or in a printed form.

Latest Stories
Cloud Expo, Inc. has announced today that Andi Mann returns to 'DevOps at Cloud Expo 2017' as Conference Chair The @DevOpsSummit at Cloud Expo will take place on June 6-8, 2017, at the Javits Center in New York City, NY. "DevOps is set to be one of the most profound disruptions to hit IT in decades," said Andi Mann. "It is a natural extension of cloud computing, and I have seen both firsthand and in independent research the fantastic results DevOps delivers. So I am excited to help the great t...
Rapid innovation, changing business landscapes, and new IT demands force businesses to make changes quickly. In the eyes of many, containers are at the brink of becoming a pervasive technology in enterprise IT to accelerate application delivery. In this presentation, attendees learned about the: The transformation of IT to a DevOps, microservices, and container-based architecture What are containers and how DevOps practices can operate in a container-based environment A demonstration of how ...
"At ROHA we develop an app called Catcha. It was developed after we spent a year meeting with, talking to, interacting with senior citizens watching them use their smartphones and talking to them about how they use their smartphones so we could get to know their smartphone behavior," explained Dave Woods, Chief Innovation Officer at ROHA, in this SYS-CON.tv interview at 19th Cloud Expo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
"Venafi has a platform that allows you to manage, centralize and automate the complete life cycle of keys and certificates within the organization," explained Gina Osmond, Sr. Field Marketing Manager at Venafi, in this SYS-CON.tv interview at DevOps at 19th Cloud Expo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
If you haven’t heard yet, CollabNet just put out some very big news for managing and gaining value from DevOps. We introduced CollabNet DevOps Lifecycle Manager (DLM) — a platform designed exclusively for providing a single pane of glass, dashboard, and traceability views across your DevOps toolchain and processes from planning to operations and that can be traced back to planning and development.
@DevOpsSummit taking place June 6-8, 2017 at Javits Center, New York City, is co-located with the 20th International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. @DevOpsSummit at Cloud Expo New York Call for Papers is now open.
SYS-CON Events announced today that Fusion, a leading provider of cloud services, will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Fusion, a leading provider of integrated cloud solutions to small, medium and large businesses, is the industry’s single source for the cloud. Fusion’s advanced, proprietary cloud service platform enables the integration of leading edge solutions in the cloud, including cloud...
Video experiences should be unique and exciting! But that doesn’t mean you need to patch all the pieces yourself. Users demand rich and engaging experiences and new ways to connect with you. But creating robust video applications at scale can be complicated, time-consuming and expensive. In his session at @ThingsExpo, Zohar Babin, Vice President of Platform, Ecosystem and Community at Kaltura, discussed how VPaaS enables you to move fast, creating scalable video experiences that reach your aud...
Regulatory requirements exist to promote the controlled sharing of information, while protecting the privacy and/or security of the information. Regulations for each type of information have their own set of rules, policies, and guidelines. Cloud Service Providers (CSP) are faced with increasing demand for services at decreasing prices. Demonstrating and maintaining compliance with regulations is a nontrivial task and doing so against numerous sets of regulatory requirements can be daunting task...
With major technology companies and startups seriously embracing IoT strategies, now is the perfect time to attend @ThingsExpo 2016 in New York. Learn what is going on, contribute to the discussions, and ensure that your enterprise is as "IoT-Ready" as it can be! Internet of @ThingsExpo, taking place June 6-8, 2017, at the Javits Center in New York City, New York, is co-located with 20th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry p...
@DevOpsSummit at Cloud taking place June 6-8, 2017, at Javits Center, New York City, is co-located with the 20th International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is no time to wait for long developm...
In his keynote at 18th Cloud Expo, Andrew Keys, Co-Founder of ConsenSys Enterprise, provided an overview of the evolution of the Internet and the Database and the future of their combination – the Blockchain. Andrew Keys is Co-Founder of ConsenSys Enterprise. He comes to ConsenSys Enterprise with capital markets, technology and entrepreneurial experience. Previously, he worked for UBS investment bank in equities analysis. Later, he was responsible for the creation and distribution of life sett...
Get deep visibility into the performance of your databases and expert advice for performance optimization and tuning. You can't get application performance without database performance. Give everyone on the team a comprehensive view of how every aspect of the system affects performance across SQL database operations, host server and OS, virtualization resources and storage I/O. Quickly find bottlenecks and troubleshoot complex problems.
DevOps is being widely accepted (if not fully adopted) as essential in enterprise IT. But as Enterprise DevOps gains maturity, expands scope, and increases velocity, the need for data-driven decisions across teams becomes more acute. DevOps teams in any modern business must wrangle the ‘digital exhaust’ from the delivery toolchain, "pervasive" and "cognitive" computing, APIs and services, mobile devices and applications, the Internet of Things, and now even blockchain. In this power panel at @...
The 20th International Cloud Expo has announced that its Call for Papers is open. Cloud Expo, to be held June 6-8, 2017, at the Javits Center in New York City, brings together Cloud Computing, Big Data, Internet of Things, DevOps, Containers, Microservices and WebRTC to one location. With cloud computing driving a higher percentage of enterprise IT budgets every year, it becomes increasingly important to plant your flag in this fast-expanding business opportunity. Submit your speaking proposal ...