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LEAD SUPERVISORs:   PROF TIMOTHY DENISON, NUFFIELD DEPARTMENT OF CLINICAL NEUROSCIENCES and Prof Colin EspieNUFFIELD DEPARTMENT OF CLINICAL NEUROSCIENCES

Co-supervisors: Dr Simon Kyle, Nuffield Department of Clinical Neurosciences, Dr Hayriye Cagnan, Nuffield Department of Clinical Neurosciences, Assoc Prof Alex GreenNuffield Department of Clinical Neurosciences

Commercial partner: Bioinduction Ltd, 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 CADET 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); CADET: centromedian thalamus (CMT)) that couple into the reticular activating network and are being explored as therapeutic targets.

This collaboration aids Bioinduction, Oxford, and the MRC:

Bioinduction: The technical organization at Bioinduction will be exposed to advanced closed-loop algorithm concepts and bi-directional-interfacing methods. These capabilities will assist them with their product development roadmap. They will also be exposed to various stimulation strategies for disease management that will help build their therapy pipeline.

Oxford: The combined engineering, medical, and basic neuroscience teams will have unique access to the human nervous system (1) to evaluate the impact of brain stimulation on sleep biomarkers and (2) to develop circadian responsive brain stimulation. The ability to leverage Bioinduction’s manufacturing and quality management systems will also facilitate first-in-man trials through our collaboration with the surgical team (collaborators Prof Aziz and Prof Green).

MRC: This project aligns with the MRC objectives of whole organism (human) research using quantitative, multidisciplinary methods, while furthering the strategies of advanced therapies, translational development, and precision healthcare in the industrial sector.

 

Apply using course: DPhil in Clinical Neurosciences

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