Non-invasive dynamic neural control by laser-based technology

Europe faces an enormous human toll of brain disorders, with an estimated 83 million people affected, and economic costs amounting to approximately €800 billion. Drug treatments for brain disorders prove often less than effective with a lack of selective cell targeting. A failure to develop new drugs has led major Pharmaceutical companies to withdraw from CNS drug development in recent years. Methods such as Transcranial Magnetic Stimulation or Deep Brain Stimulation have displayed some therapeutic efficacy, however they are non-selective and/or invasive. It is therefore clear that with a failure of conventional therapy, a new approach is necessary, and development of new technology. NEUROPA will directly tackle this issue. An ideal treatment would be one where activity in specific implicated neuronal networks could be selectively modulated. To be relevant to human disorders the therapy should enable the long-term modulation of dysfunctional networks. For potential widespread use in patients the intervention and monitoring of effects on network activity should also be non-invasive. NEUROPA will develop a new Phytoptogenetics technology: novel Phytochromes that will enable modulation of expression of specific genes, selectively and non-invasively delivered and targeted to cortical neurons in specific cortico-subcortical loops. Novel compact laser sources and a Diffusing Wave Spectroscopy monitoring system will be developed to enable non-invasive bidirectional control of the phytochromes by two-photon excitation. NEUROPA will achieve in-lab technology validation of long-term network activity modulation and behavioural symptom alleviation in Huntington’s and Alzheimer’s disease mouse models. To achieve this, we have assembled a consortium of phytochrome engineering, gene delivery, laser photonics and detection experts, cellular, in vivo and behavioural neuroscientists, together with drug discovery expertise. We envisage progress to human use within 15 years.