Date: 2012-10-02
Type of information: Grant
Company: Addex Therapeutics (Switzerland)
Investors: Commission for Technology and Innovation (CTI) (Switzerland)
Amount: CHF700,000 (€578 600)
Funding type: grant
Planned used: This grant wil be used to fund the development of allosteric modulator therapeutics for neurodegenerative and psychiatric diseases.
Others: Addex Therapeutics, a company pioneering allosteric modulation-based oral small molecule drug discovery and development, has been awarded a CHF700,000 grant from the Swiss Commission for Technology and Innovation (CTI) to develop allosteric modulator therapeutics for neurodegenerative and psychiatric diseases. Addex will collaborate with the Center for Psychiatric Neuroscience at the University of Lausanne and at the Laboratory for the Study of Neurodegenerative Diseases (LEN) at Ecole Polytechnique Fédérale de Lausanne (EPFL).
The objective of the project is the characterization and optimization of potent and selective allosteric modulators targeting Group III of metabotropic glutamate receptors, mGluR4 and mGluR7. Drug candidates targeting mGluR4 will be assessed in animal models replicating human Parkinson\'s disease. Electrophysiological studies will be carried out with allosteric modulators targeting both mGluR4 and mGluR7 to investigate their role in modulating synaptic transmission. Data from the project will contribute to the selection of the best candidate compounds for clinical development.
Addex is currently characterizing a number of novel, selective, orally available mGluR4 positive allosteric modulators (PAMs), which have demonstrated efficacy in several different rodent models of Parkinson\'s disease, anxiety and most recently in the industry standard neuroinflammation model of multiple sclerosis, the Relapsing-Remitting Experimental Allergic Encephalomyelitis (RR-EAE) model. Addex is currently advancing this lead series towards identification of a clinical candidate compound. The Company\'s mGluR7 negative allosteric modulator (NAM) program is currently in lead optimization phase where compounds representing multiple chemical series have been shown to be efficacious in animal models of anxiety. There are currently no described mGluR7 NAM compounds and therefore Addex is uniquely positioned to potentially unravel the role of this receptor in the brain.
The mGluR4 belongs to the Group III mGluRs (Class C G-Protein Coupled Receptor) and is negatively coupled to adenylate cyclase via activation of the Gai/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, anxiety, neuropathic and inflammatory pain, schizophrenia and diabetes.
The mGluR7 receptor is the most highly conserved of all mGluR subtypes, exhibiting the widest distribution in the brain. It is localized pre-synaptically at a broad range of glutamatergic and GABAergic synapses and is thought to be one of the most important mGluR subtypes in regulating CNS function. Preclinical data suggest that mGluR7 antagonism could alleviate stress-related anxiety and depressive symptoms and deficits in amygdala-dependent behaviors (fear response and conditioned taste aversion). These data are consistent with the abundant localization of mGluR7 in brain regions involved in the control of fear and emotion.
Therapeutic area: Neurodegenerative diseases - Psychiatric diseases
