Temperature InduCed K+ channel as a tool to treat neuropathic pain: TICK

Programme(s): H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)

Topic(s): ERC-2020-POC - Call for proposals for ERC Proof of Concept Grant

Call for proposal: ERC-2020-PoC

Funding Scheme: ERC-POC-LS - ERC Proof of Concept Lump Sum Pilot

Grant agreement ID: 966841

Objective:
Non-invasive Control of Neuronal Activity can in principle contribute to the medical treatment of pathologic states in which the electrical activity of neurons is impaired, as in seizures and in chronic pain (CP). To this end, we are developing and validating proteins regulated by non-toxic external stimuli that freely penetrate tissues. TICK (Temperature InduCed K+ channel) is a K+ Channel reversibly regulated by Temperature in a very narrow range (37-40 °C). The open channel drives a large K+ efflux that hyperpolarizes the neuronal cell and prevents action potential firing. The effect is reversible and the channel closes when the temperature drops below 40°C. The perfect match with the temperature requirement for humans, prompts us to consider TICK as a promising medical tool for neuronal inhibition, in the treatment of CP. Chronic pain (CP) is a medical condition affecting around 20% of adults in Europe, characterised by an abnormal duration of pain (> 12 weeks). CP is extremely hard to treat, with only about half of patients reporting adequate pain relief. This situation is even worse for neuropathic pain (NP), a specific class of CP affecting 8% of global population, which leads the brain to interpret as pain normally non-painful stimuli. NP is difficult to treat and to diagnose, due to the large number of entities involved (cells, genes and proteins working in synergy). Drugs targeting the central nervous system (e.g. antidepressants and opioids) provide only partial pain relief and are nonspecific, also causing side effects like addiction and nausea, thus restraining their adoption for prolonged treatments. TICK has no side effects and also overcomes the unavoidable limit of similar optogenetic treatment previously proposed: the need of fiber optic implant to bring light. The first version of these channels, has already been tested preliminary on rats. During this project we plan to further validate the treatment and explore its commercial potential.