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Development of a bioelectronic system for applying chronobiology to improve the treatment of neurological disorders

Lead supervisors: Prof Tim Denison, Department of Engineering Science, and prof Colin espie, Nuffield Department of Clinical Neurosciences

Co-supervisor: Assoc Prof Hayriye Cagnan & Assoc Prof Simon Kyle, Nuffield Department of Clinical Neurosciences

Commercial partner: Bioinduction, Bristol

 

The emerging field of “bioelectronics” provides novel therapies by sensing and electrically stimulating the nervous system. Bioelectronic systems are used currently for deep brain stimulation (DBS) in Parkinson’s and epilepsy; whilst sleep disorders are a common co-morbidity of these neurological disorders, DBS does not currently account for sleep in therapy optimization.

We aim to develop circadian rhythm responsive brain stimulation algorithms using the “DyNeuMo” research system - a highly-configurable, implantable bioelectronic platform for studying human subjects with neurological disorders. This project is a collaborative effort with Bioinduction Ltd., and builds upon their existing Picostim implant infrastructure. The DyNeuMo adds scientific instrumentation to this implant to determine how electrical stimulation impacts the nervous system and to develop novel stimulation strategies tailored to patient’s needs.

Specifically, the DyNeuMo system supports deep brain stimulation, while enabling research through:

  • Long-term (24/7) access to neural networks in real-world environments, providing insights into circadian rhythms, and disease progression;
  • Deterministic probing of neural networks with stimulation, elucidating their mechanisms of action;

The specific objective of this project is to characterize the impact of neural stimulation on patients’ sleep architecture and implement circadian rhythm responsive therapies. Using the research toolkit provided by the DyNeuMo system we will 1) acquire and analyze data from the implant and characterize how physiological markers linked to sleep respond to stimulation, 2) develop and test circadian rhythm responsive stimulation protocols.

The DyNeuMo system recently received the MHRA approval for both humanitarian use cases (cervical dystonia) and an Oxford-sponsored device trial, MINDS, in multiple system atrophy (Green and Denison). The MINDS trial lays the groundwork for exploring circadian-based stimulation therapies, and the existing medical design files and regulatory paperwork provide a template for additional therapy concepts in epilepsy, cardiac (e.g. hypertension) and other autonomic diseases. Our initial focus will be on supporting the MINDS trial and the CEMENT trial for Lennox-Gastaut in collaboration with Great Ormond Street and King’s. These device trials focus on key networks in the nervous system (MINDS): pedunculopontine nucleus (PPN); CEMENT: centromedian thalamus (CMT) that couple into the reticular activating network and are being explored as therapeutic targets.

 

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