Addex Initiates New Study in Collaboration with US National Institute of Drug Abuse with ADX88178 in Non-Human Primate Model of Cocaine Addiction
Geneva, Switzerland, 11 October 2016 – Addex Therapeutics (SIX: ADXN) announced today it has initiated a new study with ADX88178, a metabotropic subtype 4 (mGlu4) receptor positive allosteric modulator (PAM), in a non-human primate model of cocaine self-administration. The study is being conducted through the Company’s ongoing research collaboration with the US National Institute of Drug Abuse (NIDA).
The effect of acute treatment with ADX88178 on intravenous (IV) cocaine self-administration will be determined in rhesus monkeys that self-administer varying doses of cocaine. The study will initially seek to determine effects of the compound on 0.40 mg/kg cocaine discrimination. Following this, a dose-ranging study will aim to determine which dose is most effective against IV 0.03 mg/kg/injection cocaine reinforcement in individual monkeys. Once the most effective dose of ADX88178 is identified for each individual, the compound will be tested against a full cocaine dose-effect curve (0.001–0.1 mg/kg/injection, IV).
“We are very pleased with our collaboration with NIDA that generated earlier this year compelling data with ADX71441, our GABA B PAM, in the same model of cocaine seeking behavior,” said Robert Lütjens, Head of Discovery at Addex. “This study will be the first time that an mGluR4PAM has been tested in a non-human primate model of cocaine addiction and will provide invaluable data on the potential of this therapeutic target in what is a major public health problem.”
About Drug Abuse and Drug Addiction
Scientific advances have revolutionized our understanding of addiction as a chronic, relapsing disease and not a moral failure. Drug addiction is a complex illness which is characterized by intense and, at times, uncontrollable drug craving, along with compulsive drug seeking and use that persist even in the face of devastating consequences. Addiction affects multiple brain circuits, including those involved in reward and motivation, learning and memory, and inhibitory control over behavior. While a person initially chooses to take drugs, over time the effects of prolonged exposure on brain functioning compromise that ability to choose, and seeking and consuming the drug become compulsive, often eluding a person’s self-control or willpower. Because drug abuse and addiction have so many dimensions and disrupt so many aspects of an individual’s life, treatment is not simple. Addiction treatment must help the individual stop using drugs, maintain a drug-free lifestyle, and achieve productive functioning in the family, at work, and in society. Patients typically require long-term or repeated episodes of care to achieve the ultimate goal of sustained abstinence and recovery of their lives.
The mGlu4 receptor belongs to the Group III mGluRs (Class C G-Protein Coupled Receptor) and is negatively coupled to adenylate cyclase via activation of the Gαi/o protein. It is expressed primarily on presynaptic terminals, functioning as an autoreceptor or heteroceptor and its activation leads to decreases in neurotransmitter release from presynaptic terminals. The mGluR4 is uniquely distributed in key brain regions involved in multiple CNS disorders. In particular, mGluR4 is abundant in striato-pallidal synapses within the basal ganglia circuitry a key area implicated in movement disorders, like Parkinson’s disease. In the immune system mGluR4 has been found on dendritic cells (DCs). Emerging data implicate mGluR4 in multiple indications such as multiple sclerosis, Parkinson’s disease, addiction, anxiety, neuropathic and inflammatory pain, schizophrenia and diabetes.
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a biopharmaceutical company focused on the development of novel, orally available, small molecule allosteric modulators for neurological disorders. Addex lead drug candidate, dipraglurant (mGluR5 negative allosteric modulator or NAM) has successfully completed a phase IIa POC in Parkinson’s disease levodopa-induced dyskinesia (PD-LID), and is being prepared to enter phase III for PD-LID with support from the Michael J. Fox Foundation for Parkinson’s Research (MJFF). In parallel, dipraglurant’s therapeutic use in dystonia is being investigated with support from the Dystonia Medical Research Foundation (DMRF). Addex second clinical program, ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc for epilepsy. In addition, ADX71441 (GABAB receptor PAM) has received regulatory approval to start phase I and is being investigated for its therapeutic use in Charcot-Marie-Tooth Type 1A disease (CMT1A), cocaine and alcohol use disorder and nicotine dependence. Discovery programs include mGluR4PAM for neurodegenerative diseases, mGluR7NAM for psychosomatic disorders and TrkBPAM for neurodegenerative disorders which are being advanced in collaboration with the Universities of Lausanne and Geneva under the Swiss CTI grant program; and mGluR3PAM which is being advanced in collaboration with Pierre Fabre Pharmaceuticals. Allosteric modulators are an emerging class of small molecule drugs which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. Addex allosteric modulator drug discovery platform targets receptors and other proteins that are recognized as essential for therapeutic intervention – the Addex pipeline was generated from this pioneering allosteric modulator drug discovery platform.
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Disclaimer / Forward-looking statements: This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Addex Therapeutics Ltd. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements.