Neural Interfaces towards a Treatment of Epilepsy – Merging Photopharmacology with Implantable Optoelectronics and Electrophoretic Drug Delivery

• Applicant: Dr. Johannes Gurke
• Subject Area: Electronic Semiconductors, Components and Circuits, Integrated Systems, Sensor Technology, Theoretical Electrical Engineering ; Biological and Biomimetic Chemistry ; Cognitive, Systems and Behavioural Neurobiology
• Term: from 2019 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 427938672

Interfacing with the human brain is a critical challenge for a deep understanding of neuronal processes and is the key for medicinal progress in treatment of neurological diseases, like epilepsy. An imbalance between excitatory and inhibitory signals has been discussed as a reason for epileptic seizures. The incorporation of an intracortical injection of anticonvulsants, bypassing obstacles like the blood–brain barrier, and a close-by measurement of neuronal activity is a promising therapeutic strategy. The diffusion of the drug after its electrophoretic, "dry" delivery via an organic ion pump in the targeted brain area limits the temporal resolution of this approach. This circumstance is aggravated by the fact that the exact prediction of seizure’s occurrence and intensity is still out reached, even though precise, intracortical measurements of the brain activity are possible. This makes a high temporal control over the antiseizure drug concentration within the target area even more important. The use of light appears to be a potent way to accomplish such a control, due to its non-invasive, harmless nature and achievement of high spatial and temporal resolution. The concept of photopharmacology is based on the structural interconnection of pharmacologic active agents with molecular photoswitches. Extensive studies on photoswitchable excitatory as well as inhibitory neurotransmitters for use in the central nervous system have been conducted, using light to reversibly de-/activate the pharmacological effect of the drug. The momentum in the field of optogenetics led to a wide range of implantable optoelectronic probes for in vivo illumination of biologic tissue.The merging of those disciplines, namely: photopharmacology, intracortical injection and measurement as well as implantable optoelectronics, might overcome the problems of each individual approach and provide a powerful tool for antiseizure therapy. To achieve this, light emitting diodes will be integrated in an implant with a flexible, organic electrode and a microfluidic ion pump, injecting a photoswitchable antagonist of a glutamate receptor. A constant monitoring of the neural activity by the device will allow the prediction of the seizure’s likelihood. If the forecast indicates an increased likelihood of an epileptic event inactive drug will be injected, having no effect on the neural activity. In case of actual seizure, red light irradiation will occur on demand, suppressing active potential firing by inhibiting the signal transmission in the glutamatergic synapses. Depending on the measured intensity of the seizure, the pharmacologically active drug concentration within the tissue will be increased by red light or decreased by blue light illumination, respectively, affording precise control.The integration of all system components in an implant, in particular its design, microfabrication, characterization and optimization towards the application will be the main task of this project

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. George Malliaras