Translational Bioengineering for Neurological Disorders
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
The total economic cost of neurological disorders exceeds £100B per annum in the UK. The emerging field of “bioelectronics” provides a novel approach to intervention, by using electronic
hardware to directly stimulate the nervous system with physiologically-inspired electrical signals. Given the processing capability of electronics and precise targeting of electrodes, the potential advantages of bioelectronics include specificity in time, method, and location of treatment, with the ability to iteratively refine and update therapy algorithms in software.
This programme focuses on the design and prototyping of bi-directional, bioelectronic brain-interface-technology, including hardware and algorithm frameworks for closed-loop systems, that enables the research and translation of treatments for neurological disorders with lower invasiveness and cost. The programme follows a staged deployment of resources: initial learning from research systems in the first-half of the programme will be applied to develop the next-generation of brain-interface technologies, which will be validated in pilot trials in the second half of the program. This approach captures the iterative nature of medical technology and mitigates technical and clinical risks.
The outcomes of this programme will inform the clinical translation of adaptive brain modulation systems for Parkinson’s, epilepsy, and their sleep comorbidities.
hardware to directly stimulate the nervous system with physiologically-inspired electrical signals. Given the processing capability of electronics and precise targeting of electrodes, the potential advantages of bioelectronics include specificity in time, method, and location of treatment, with the ability to iteratively refine and update therapy algorithms in software.
This programme focuses on the design and prototyping of bi-directional, bioelectronic brain-interface-technology, including hardware and algorithm frameworks for closed-loop systems, that enables the research and translation of treatments for neurological disorders with lower invasiveness and cost. The programme follows a staged deployment of resources: initial learning from research systems in the first-half of the programme will be applied to develop the next-generation of brain-interface technologies, which will be validated in pilot trials in the second half of the program. This approach captures the iterative nature of medical technology and mitigates technical and clinical risks.
The outcomes of this programme will inform the clinical translation of adaptive brain modulation systems for Parkinson’s, epilepsy, and their sleep comorbidities.
Technical Summary
The evolution of adaptive brain stimulation is at a critical stage of translation, and several factors should be considered during the transition to the clinic. Given its potential, feedback approaches are being piloted for use in multiple disease states. Proof-of-concept experiments to improve Parkinson’s DBS with feedback control show promise, but are still restricted to short trials (order of hours) in the clinic and are burdensome to configure. In addition, attempts at feedback control for epilepsy have arguably proved disappointing, and yield modest improvement over open-loop approaches. From a control systems perspective, these initial efforts focused more on “exploitation” of existing stimulation techniques with simple feedback, versus principled application of control methods to systematically “explore” the available neuroscience parameter space. Similar issues are raised with minimally-invasive approaches like transcranial magnetic stimulation (TMS), where the optimal design of stimulation parameters still remains an open question. Due in part to this limited performance and complexity, feedback systems have thus far had limited clinical impact.
The Translational Bioengineering programme aims to address these shortcomings. The inter-linked themes for the programme are 1) improving the capability of invasive “neural coprocessors” (neurostimulation systems with algorithmic capabilities embedded), 2) expanding the coprocessor concept to include minimally invasive systems, with an emphasis on brain-state dependent stimulation and synchronized integration with implants, and 3) piloting these technologies in neuroscience studies that address key gaps in translation. For both invasive and non-invasive neural coprocessors and operating systems, emphasis will be placed on 1) improving sense-stimulation performance to enhance closed-loop performance, 2) improving the data gathering and algorithm capability through advanced wireless telemetry and distributed computational methods, and 3) further advancing the research infrastructures, including regulatory and risk management, to enable collaboration and modular research tool development.
To deploy and test these research systems, we will work collaboratively within the MRC BNDU to 1) pilot chronic adaptive stimulation concepts in movement disorders, epilepsy, and mood disorders in collaboration with the OpenMind consortium, 2) test brain-state dependent feedback and network plasticity methods using paired association enabled by our new instrumentation, and 3) design adaptive algorithms for modulating and improving sleep quality to address this common co-morbidity for neurological disorders.
Given the emphasis on translation across multiple brain disorders, significant elements of the proposed research involve UK and US collaborators, industry partners, and regulators. The work in this proposal will follow a scaled Quality Management System compliant to key aspects of ISO13485 in a research environment, with an emphasis on IEC 60601-1 (essential safety), 60601-1-10 (physiologic control systems), 60601-2-10 (neurostimulation), and ISO14971 (risk). Data security aligns to EU General Data Protection Regulations.
The Translational Bioengineering programme aims to address these shortcomings. The inter-linked themes for the programme are 1) improving the capability of invasive “neural coprocessors” (neurostimulation systems with algorithmic capabilities embedded), 2) expanding the coprocessor concept to include minimally invasive systems, with an emphasis on brain-state dependent stimulation and synchronized integration with implants, and 3) piloting these technologies in neuroscience studies that address key gaps in translation. For both invasive and non-invasive neural coprocessors and operating systems, emphasis will be placed on 1) improving sense-stimulation performance to enhance closed-loop performance, 2) improving the data gathering and algorithm capability through advanced wireless telemetry and distributed computational methods, and 3) further advancing the research infrastructures, including regulatory and risk management, to enable collaboration and modular research tool development.
To deploy and test these research systems, we will work collaboratively within the MRC BNDU to 1) pilot chronic adaptive stimulation concepts in movement disorders, epilepsy, and mood disorders in collaboration with the OpenMind consortium, 2) test brain-state dependent feedback and network plasticity methods using paired association enabled by our new instrumentation, and 3) design adaptive algorithms for modulating and improving sleep quality to address this common co-morbidity for neurological disorders.
Given the emphasis on translation across multiple brain disorders, significant elements of the proposed research involve UK and US collaborators, industry partners, and regulators. The work in this proposal will follow a scaled Quality Management System compliant to key aspects of ISO13485 in a research environment, with an emphasis on IEC 60601-1 (essential safety), 60601-1-10 (physiologic control systems), 60601-2-10 (neurostimulation), and ISO14971 (risk). Data security aligns to EU General Data Protection Regulations.
Organisations
- University of Oxford (Lead Research Organisation)
- Brown University (Collaboration)
- Mayo Clinic (Collaboration)
- Bioinduction (Collaboration)
- University of Surrey (Collaboration)
- Great Ormond Street Hospital (GOSH) (Collaboration)
- University of California, San Francisco (Collaboration)
- THE MAGSTIM COMPANY LIMITED (Collaboration)
- KING'S COLLEGE LONDON (Collaboration)
People |
ORCID iD |
Publications
Baker JL
(2023)
Regulation of arousal and performance of a healthy non-human primate using closed-loop central thalamic deep brain stimulation.
in International IEEE/EMBS Conference on Neural Engineering : [proceedings]. International IEEE EMBS Conference on Neural Engineering
Beale R
(2022)
OxVent: Design and evaluation of a rapidly-manufactured Covid-19 ventilator.
in EBioMedicine
Denison T
(2022)
Neuromodulation in 2035: The Neurology Future Forecasting Series.
in Neurology
Duchet B
(2023)
How to entrain a selected neuronal rhythm but not others: open-loop dithered brain stimulation for selective entrainment
in Journal of Neural Engineering
Fleming JE
(2022)
Embedding digital chronotherapy into bioelectronic medicines.
in iScience
Gilron R
(2021)
Long-term wireless streaming of neural recordings for circuit discovery and adaptive stimulation in individuals with Parkinson's disease.
in Nature biotechnology
Gregg NM
(2021)
Thalamic deep brain stimulation modulates cycles of seizure risk in epilepsy.
in Scientific reports
Kavoosi A
(2022)
Computationally efficient neural network classifiers for next generation closed loop neuromodulation therapy - a case study in epilepsy.
in Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
Related Projects
| Project Reference | Relationship | Related To | Start | End | Award Value |
|---|---|---|---|---|---|
| MC_UU_00003/1 | 01/04/2020 | 31/03/2025 | £1,280,000 | ||
| MC_UU_00003/2 | Transfer | MC_UU_00003/1 | 01/04/2020 | 31/03/2025 | £2,361,000 |
| MC_UU_00003/3 | Transfer | MC_UU_00003/2 | 01/04/2020 | 31/03/2025 | £1,126,000 |
| MC_UU_00003/4 | Transfer | MC_UU_00003/3 | 01/04/2020 | 31/03/2025 | £2,269,000 |
| MC_UU_00003/5 | Transfer | MC_UU_00003/4 | 01/04/2020 | 31/03/2025 | £2,274,000 |
| MC_UU_00003/6 | Transfer | MC_UU_00003/5 | 01/04/2020 | 31/03/2025 | £2,177,000 |
| Description | Chairman of Strategic Interest Group (SIG) for the Knowledge Transfer Network (KTN) exploring Neurotechnology |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Neurotechnology, "the application of engineering to the human nervous system" is undergoing rapid advancements, thanks to significant progress in a number of key research areas; from neuroscience, through computing power to AI, imaging, materials technology, sensors and manufacturing. This has been recognised internationally, with significant public and private investment being made. The US government alone has invested $1.8bn since 2013 and other nations have since joined this global effort. Our understanding of how the brain functions, and how technology can interface with it, has progressed dramatically, with significant clinical impact rapidly emerging. In the clinical arena, innovation in neurotechnology will impact millions of patients with physical disabilities, neurological diseases, mental health disorders and related conditions. Many of these patients are currently beyond the reach of pharmacology and other therapeutic methods. The purpose of this working group is to make the case for a major investment in this area so that the UK can take the international lead in neurotechnology; championing its ethical adoption and becoming home to the next generation of technology giants, in the mould of Deep Mind or Arm. |
| URL | https://ktn-uk.org/wp-content/uploads/2021/06/A-transformative-roadmap-for-neurotechnology-in-the-UK... |
| Description | Neurotechnology in and for society: Deliberation, stewardship and trust |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Contribution to a national consultation/review |
| Impact | Neurotechnology has great potential for improving societal health and well-being. Yet, just as with many other emerging technologies, it faces ethical, legal, and social challenges (ELSI). In the absence of international instruments in this field, the OECD Council adopted a Recommendation on Responsible Innovation in Neurotechnology in December 2019. An event held in Seoul in September 2020 was the first in a series of workshops that set out to support adherents to implement the Recommendation. The event explored a number of themes and potential modes - including options for monitoring the implementation and use of the Recommendation, mapping institutions and actors in Korea, discussing options for institutional capacity building and fostering dialogue and dissemination of the Recommendation. A key finding was a strong desire for more interdisciplinary collaboration between neuroscientists, neuroethicists and experts in other fields. In addition, the convergence of neurotechnology with other emerging technologies as well as resulting ELSI concerns on the use of brain data were reoccurring themes. This two-day workshop in May 2021 is hosted by the Swiss Delegation. It builds on the discussions at the Seoul event and focuses on issues of societal deliberation, stewardship and trust that are vital in the notion of Neurotechnology in and for society. Unlike the broad aim of the Seoul workshop at building capacity to implement the Recommendation, it takes a narrower approach by focussing on Principle 5 (Enable societal deliberation on neurotechnology) and Principle 8 (Promote cultures of stewardship and trust in neurotechnology across the public and private sector) in the Recommendation. Zurich event objectives Share initiatives, good practices and experiences related to Principles 5 and 8 of the Recommendation; Engage stakeholders in a critical discussion on what worked and what needs to be improved to implement the Recommendation; Explore how the Recommendation fits with and could be implemented in national and transnational activities in the future; Generate insights which inform guidance resources for adherents and fuel future discussions. Principle 5: Enable societal deliberation on neurotechnology In order to enable such deliberation, relevant actors should: a) Promote open communication across expert communities and with the public to promote neurotechnology literacy and the exchange of information and knowledge. b) Engage in multi-stakeholder dialogues and deliberation to ensure diverse inputs into decision making processes, public policy and governance. c) Ensure that the results of formal dialogues are considered and taken into account in decision- making wherever possible. d) Ensure processes for engaging stakeholders are fair, transparent, and predictable. e) Encourage transparent processes of technology appraisal to deepen and inform public debate about the longer-term trajectory of neurotechnology |
| URL | http://www.oecd.org/science/emerging-tech/neurotechnology-in-and-for-society.htm |
| Description | US BRAIN Initiative steering group |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Membership of a guideline committee |
| Impact | The Advisory Committee to the NIH Director BRAIN Initiative® Working Group 2.0, formed in April 2018, worked tirelessly to assess BRAIN's progress and advances within the context of the original BRAIN 2025 report, identify key opportunities to apply new and emerging tools to revolutionize our understanding of brain circuits, and designate valuable areas of continued technology development. Over the course of 1.5 years, the Working Group 2.0 has undertaken a deliberative and open process consisting of portfolio review, scientific workshops, town halls, and public solicitation. Continuing in this manner, the Working Group 2.0 shared with the community its inital thoughts on the current state of The BRAIN Initiative®, including opportunities for keeping pace with the evolving scientific landscape, as well as the identification of new opportunities for research and technology development, within a solid ethical framework, to ensure BRAIN Initiative research is of the utmost value to the public it intends to serve. Following a 30-day public comment period, the Working Group 2.0 reviewed all responses as they iterated the Report to the Advisory Committee to the NIH Director (ACD) for consideration at its meeting on June 14th, 2019. After receiving feedback from the ACD and the NIH Director, the Working Group 2.0 again presented the report to the ACD via teleconference on October 21, 2019. The report, The BRAIN Initiative® 2.0: From Cells to Circuits, Toward Cures, was endorsed by the ACD. NIH Director, Dr. Francis Collins accepted the ACD endorsed report and NIH will carefully consider how to integrate the findings of The BRAIN Initiative® 2.0: From Cells to Circuits, Toward Cures in future BRAIN Initiative priorities and investments. |
| URL | https://braininitiative.nih.gov/strategic-planning/acd-working-groups/brain-initiative%C2%AE-20-cell... |
| Description | OpenMind consortium for creating and disseminating research tools for first-in-human trials |
| Amount | $4,400,000 (USD) |
| Funding ID | 1U24NS113637 |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 08/2020 |
| End | 08/2024 |
| Title | The "DyNeuMo-1" Active Implantable Research System: Motion and Circadian Adaptive Neurostimulator for First-in-Human Research Studies |
| Description | There is growing interest in using adaptive neuromodulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the `DyNeuMo Mk-1', a fully-implantable, adaptive research stimulator that titrates stimulation based on circadian rhythms (e.g. sleep, wake) and the patient's movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability, and relatively modest cost. The DyNeuMo Mk-1 system was designed, manufactured and verified using ISO\,13485 design controls, including ISO\,14971 risk management techniques to ensure patient safety, while enabling novel algorithms. The system was validated for an intended use case in movement disorders under an emergency-device authorization from the MHRA. The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as shocks for urinary incontinence. With appropriate design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | The DyNeuMo-1 is now MHRA approved for first-in-human clinical studies exploring the treatment of multiple system atrophy (Parkinson's like state). This trial will be run at Oxford with first implants in March 2021. Pending success in this trial, the tool is being made available to other UK researchers as a platform research tool. Note that this project is a collaboration with a UK SME Bioinduction Ltd, and their subsidiary Finetech Medical, who are the only certified manufacturers for active medical implants in the UK. |
| URL | https://www.biorxiv.org/content/10.1101/2020.09.10.292284v1 |
| Title | The "DyNeuMo-2" Active Implantable Research System: Electrophysiological and Circadian Adaptive Neurostimulator for First-in-Human Research Studies |
| Description | Deep brain stimulation (DBS) for Parkinson's disease, essential tremor and epilepsy is an established palliative treatment. DBS uses electrical neuromodulation to suppress symptoms. Most current systems provide a continuous pattern of fixed stimulation, with clinical follow-ups to refine settings constrained to normal office hours. An issue with this management strategy is that the impact of stimulation on circadian, i.e. sleep-wake, rhythms is not fully considered; either in the device design or in the clinical follow-up. Since devices can be implanted in brain targets that couple into the reticular activating network, impact on wakefulness and sleep can be significant. This issue will likely grow as new targets are explored, with the potential to create entraining signals that are uncoupled from environmental influences. To address this issue, we have designed a new brain-machine-interface for DBS that combines a slow-adaptive circadian-based stimulation pattern with a fastacting pathway for responsive stimulation, demonstrated here for seizure management. In preparation for first-in-human research trials to explore the utility of multi-timescale automated adaptive algorithms, design and prototyping was carried out in line with ISO risk management standards, ensuring patient safety. The ultimate aim is to account for chronobiology within the algorithms embedded in brain-machine-interfaces and in neuromodulation technology more broadly. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | Trial is now funded and being planned in collaboration with Great Ormond Street Hospital and King's College for Lennox-Gastaut epilepsy. This was funded for £450,000 for a 22 subject clinical study (LifeArc). Additional clinical trials are being explore for chronic pain at Oxford. This was funded for £850,000 for a 30 subject clinical study (John Moulton Trust and Placito Trust). |
| Title | xTMS: Flexible Transcranial Magnetic Stimulation System |
| Description | The xTMS system is a programmble transcranial magnetic stimulator device. The xTMS system enables more control on the electric field pulse shape than conventional TMS device. The pTMS2 system enables PWM electric field pulse with control over the pulse shape, duration, directionality, pulse type such as mono-phasic, bi-phasic and polyphasic. It can be used in single pulse mode or repetitive TMS mode. The xTMS system requires a stimulation coil to deliver the magnetic stimulation. Brief stimuli of an electromagnetic field are applied to the neural tissues with current-carrying treatment coils. The fast-changing field induces electrical currents within the neurons and modulates cell activity. Using the xTMS device, it is possible to change the stimulus waveform and polarity of each pulse in the pulse train. It is intended for use by, or under the supervision of, a medical practitioner or investigator who has knowledge about the principles of TMS, physiology and potential side effects of TMS. It's the user's responsibility to design and validate safeness of their stimulation protocols. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | We have completed the first clinical study using the xTMS approach, and have now initiated a second study at Oxford. For this year, we are expanding to collaborations at King's College, London and Cambridge University. The studies are in publication review. Note that this project includes a collaboration with Magstim Ltd in Whitland Wales, who is supplying TMS coils for researchers to use. |
| Description | Bioinduction: DyNeuMo Research Tool co-development |
| Organisation | Bioinduction |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Project Background and Objectives The project will both 1) develop and 2) support deployment of the "DyNeuMo" research tool. DyNeuMo is a highly-configurable, implantable bioelectronic research platform for studying human subjects with diseases of the nervous system. 1) Development of DyNeuMo Research Tools Motivation for the DyNeuMo: The emerging field of "bioelectronics" can catalyse neuroscience. In addition to providing essential therapeutic stimulation, the device can support scientific instrumentation. These instruments leverage chronic access to the nervous system for unique investigations. The DyNeuMo research platform is a cranially-mounted, bioelectronic system deployable in patients undergoing surgery for deep-brain-stimulation using routine clinical procedures, and supports the existing treatments of "brain pacemakers." The DyNeuMo research tool is built on the predicate Picostim therapy system developed by Bioinduction. Adjustments to the Picostim - hardware, firmware, and software - enable new capability for exploring clinical neuroscience and prototyping new therapies. We have a roadmap of DyNeuMo systems with increasing levels of functionality. The DyNeuMo-Mk1 will add inertial sensing and motion-adaptive control to the Picostim, whilst the DyNeuMo-Mk2 will add additional bioelectrical sensing and control to the -Mk1's inertial capability. The tasks are partitioned between research system development and deployment in clinical investigations. Research Tool Development: Contributory elements may include, but are not limited to, the below. The activities will be dependent and subject to funding availability. Collaborative outputs anticipated for the DyNeuMo-Mk1 and -Mk2 research systems include: • Adaptive algorithms (both inertial- and bioelectric-based). • Configurable system updates via telemetry. • Concurrent sensing-during-stimulation • Upgraded hardware to support sensing-during-stimulation. Oxford Activities include: • ApplyCo-developing the DyNeuMo research system to explore novel therapy concepts including first-in-human clinical studies. • Support the DyNeuMo research tools through an appropriate entity (potentially a not-for-profit or Oxford spin-out focused on research platform support). •o Engaging with Bioinduction to define the design inputs and V&V requirements, including actively prototyping systems to demonstrate improved functionality for bi-directional brain interfacing in novel applications, and writing verification and validation reports to support regulatory filings. •o Developing/modify application specific interface circuits to improve the sensing and algorithm performance of the design as part of the DyNeuMo platform roadmap. •o Developing and communicateing the requirements for software/firmware changes requested by researchers to enhance research system performance and meet the aims of specific clinical protocols.. • Applying for grants based on Bioinduction estimates for software/firmware changes and systems costs (for example, Innovate UK partnership grants). •o Working with MHRA and FDA to initiate investigational studies, and NICE to characterize the QALY improvements and roadmap to translation. • Supporting the DyNeuMo research tools through an appropriate entity (potentially a not-for-profit or Oxford spin-out focused on research platform support). •o Publishing academic papers and giveing conference presentations on the DyNeuMo research platform and its clinical use cases, including outcomes. •o Research Community Engagement o? Facilitating getting the Picostim system listed on the BRAIN Platform, in addition to the DyNeuMo research systems o? Engaging with researchers to highlight the benefits of skull-mounted devices ? Introducing Bioinduction to FDA contacts for US studies o Apply for collaborative grants including Bioinduction estimates for software/firmware changes and systems costs (for example, Innovate UK partnership or Wellcome Trust technology development grants). |
| Collaborator Contribution | • Provideing access to software and hardware designs for the Picostim system sufficient for Oxford to be able to modify these designs. • Specifically provide Picostim for the duration of the Wellcome Trust project, if successful, and serveServe as the original equipment manufacturer for enhanced systems to realise the impact from such project; from hereon denoted the "DyNeuMo" platform. • Provideing engineering support and access to Bioinduction's engineering team to assist and/or collaborate with Oxford to integrate novel real time sensing and responsive stimulation hardware and software into a derivative of the existing Picostim platform. • Engage After engaging with Oxford and clinical collaborators to define design inputs for specific protocols, quoting for modifications to the software and firmware such that Oxford has sufficient information to apply for research grants. • Performing the commissioned software/firmware changes in a timely manner and performing V&V appropriate for clinical investigations per specific requirements of the clinical protocol and risk assessments. • as agreed from time to time. • Providing Regulatory and Clinical trial expertise, including access to the QMS documents as needed to complete design and development activities. • Serve as the original equipment manufacturer for the DyNeuMo research platform. • Manufacturing required DyNeuMo research systems under their QMS for clinical investigations, and supplying systems at the negotiated transfer cost. • Support applications for grant funding for specific clinical investigations.. |
| Impact | We have created two versions of the DyNeuMo research tool (described elsewhere in the tools tab). These are now supporting four clinical studies across the UK, and our collaboration also supports their SPARKS trial at Bristol Southmead. |
| Start Year | 2019 |
| Description | CADET - Children's Adaptive DBS for Epilepsy Therapy: a Multi-site Pilot Study for the Treatment of Lennox-Gastaut Epilepsy |
| Organisation | Great Ormond Street Hospital (GOSH) |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | Background: Epilepsy affects up to 1 in 240 children under the age of 16 in UK. For roughly a third of patients, medication cannot control their seizures and so alternative treatments need to be found. Lennox-Gastaut syndrome (LGS) is a particularly complex and severe childhood-onset epilepsy, characterized by multiple and concurrent seizure types and cognitive dysfunction. The prognosis for LGS is poor with 5% mortality in childhood and persistent seizures into adulthood (80%-90%). Deep brain stimulation (DBS) of the centromedian nucleus of the thalamus has been proposed as a treatment for severe epilepsy. Initial pilot studies suggest that DBS could be effective in adults and children with severe generalized epilepsies and LGS (Velasco et al, Epilepsia, 2006 Valentin et al, 2013). My prior funding has supported the development of the DyNeuMo-2 bioelectronic research system, in collaboration with the UK-SME Bioinduction, which allows for closed-loop brain stimulation. Objectives: The main aim of this pilot device trial is to perform DBS of the centromedian nucleus in four children with LGS, leveraging a key collaboration my team has established with King's College Hospital (KCH) and Great Ormond Street Hospital (GOSH). They will be the clinical trial sponsors, and I will assist with device support and co-sponsorship. The centromedian nucleus of the thalamus will be chronically stimulated with the DyNeuMo-2, with the objective of reducing the number and severity of the seizures. Consistent with my CiET milestones, the pilot study data will be used for justifying a larger trial aimed at CE-marking the system for LGS and generalized epilepsies, which are poorly served by current pharmaceutical options. Contributions by my team (we are providing the device used in the trial, the DyNeuMo-2): Recent studies suggest that Deep Brain Stimulation (DBS) of the Centromedian Nucleus of the Thalamus (CMN) may be beneficial in LGS. The clinical hypothesis in our study is that DBS in CMN has a positive risk/benefit in the treatment of children with LGS. We will evaluate the effects of CMN DBS, using a novel, rechargeable stimulator, the DyNeuMo-2 system. The DyNeuMo is a minimally-invasive, cranially-mounted device with attributes that are attractive for several applications in paediatric neuromodulation (Toth, 2020). Favourable attributes include significantly smaller size, a rechargeable battery that supports thousands of cycles (expected device longevity more than a decade), and a "physiology toolkit" that allows for objective assessment of stimulation outcomes by recording brain activity and implementation of closed-loop algorithms. A major advantage of this device is the ability for continuous stimulation which has never been done before, and is considered physiologically to have the highest potential for a good outcome. I recently secured MHRA-approval for clinical research with DyNeuMo in the MINDS trial at Oxford, and will leverage that dossier for the LGS study. |
| Collaborator Contribution | My partners are supporting the clinical plan of research: In this initial pilot clinical trial, four children with LGS (from the largest paediatric epilepsy surgery network in the UK) will be implanted with CMN DBS. To facilitate meeting the aims of this research, we have broken the plan into 4 work packages: WP 1 - Regulatory preparation (month 0-2): This work package will start with setting up a DBS system including generation of the protocol and the design dossier (clinical evidence report, device design and testing files, manufacturing) for an MHRA device-trial. Ethical approval from an NHS Research Ethics Committee (REC) will be obtained before starting recruitment. This work draws heavily from our MHRA-approved MINDS trial, and ongoing collaborations with Bioinduction. WP2 - Clinical Component (month 2-12): four patients from KCH and GOSH studied will be selected for CMN DBS. Only patients with at least 10 seizures per month in the pre-implantation period will be included in the study. All patients will undergo the following prospective study design: * Baseline period (3 months): A three-month period pre-implantation to assess history, general and neurological examination, seizure diary, ECG, EEG, neuroimaging, and patient related outcome measures (PROMs). * Post-implant recovery period (no-stimulation, 1 month): Stimulation will be turned off to study the insertion effect of the leads * Stimulation period (6 months): throughout this stage, all patients will have stimulation activated and the impact of stimulation on seizure frequency and severity assessed. WP 3 - Assessment of DBS and analysis of data (month 9-12): Seizure frequency and severity will be used to assess the effects of DBS implantation. To determine whether the numbers of clinical seizures and epileptiform discharges have been significantly reduced, a manual and an automatic analysis of interictal and ictal events before and after DBS implantation will be performed, including use of the novel physiology toolkit in the DyNeuMo. Statistical analysis will compare the number of clinical seizures, subclinical seizures and interictal discharges between pre and post DBS stimulation periods. WP 4 - Prepare for follow-on study (month 12): We will disseminate results (no restrictions), and use this pilot data to apply for a multi-centre pivotal trial grant (e.g. i4i/NIHR). |
| Impact | We have secured £53000 in direct funding based on our collaboration to start a pilot trial in Lennox-Gastaut epilepsy. This involves clinical partners, neuroscience and engineering. In 2021, we secured an additional £415,000 from LifeArc for a 22 patient clinical study. |
| Start Year | 2020 |
| Description | CADET - Children's Adaptive DBS for Epilepsy Therapy: a Multi-site Pilot Study for the Treatment of Lennox-Gastaut Epilepsy |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Background: Epilepsy affects up to 1 in 240 children under the age of 16 in UK. For roughly a third of patients, medication cannot control their seizures and so alternative treatments need to be found. Lennox-Gastaut syndrome (LGS) is a particularly complex and severe childhood-onset epilepsy, characterized by multiple and concurrent seizure types and cognitive dysfunction. The prognosis for LGS is poor with 5% mortality in childhood and persistent seizures into adulthood (80%-90%). Deep brain stimulation (DBS) of the centromedian nucleus of the thalamus has been proposed as a treatment for severe epilepsy. Initial pilot studies suggest that DBS could be effective in adults and children with severe generalized epilepsies and LGS (Velasco et al, Epilepsia, 2006 Valentin et al, 2013). My prior funding has supported the development of the DyNeuMo-2 bioelectronic research system, in collaboration with the UK-SME Bioinduction, which allows for closed-loop brain stimulation. Objectives: The main aim of this pilot device trial is to perform DBS of the centromedian nucleus in four children with LGS, leveraging a key collaboration my team has established with King's College Hospital (KCH) and Great Ormond Street Hospital (GOSH). They will be the clinical trial sponsors, and I will assist with device support and co-sponsorship. The centromedian nucleus of the thalamus will be chronically stimulated with the DyNeuMo-2, with the objective of reducing the number and severity of the seizures. Consistent with my CiET milestones, the pilot study data will be used for justifying a larger trial aimed at CE-marking the system for LGS and generalized epilepsies, which are poorly served by current pharmaceutical options. Contributions by my team (we are providing the device used in the trial, the DyNeuMo-2): Recent studies suggest that Deep Brain Stimulation (DBS) of the Centromedian Nucleus of the Thalamus (CMN) may be beneficial in LGS. The clinical hypothesis in our study is that DBS in CMN has a positive risk/benefit in the treatment of children with LGS. We will evaluate the effects of CMN DBS, using a novel, rechargeable stimulator, the DyNeuMo-2 system. The DyNeuMo is a minimally-invasive, cranially-mounted device with attributes that are attractive for several applications in paediatric neuromodulation (Toth, 2020). Favourable attributes include significantly smaller size, a rechargeable battery that supports thousands of cycles (expected device longevity more than a decade), and a "physiology toolkit" that allows for objective assessment of stimulation outcomes by recording brain activity and implementation of closed-loop algorithms. A major advantage of this device is the ability for continuous stimulation which has never been done before, and is considered physiologically to have the highest potential for a good outcome. I recently secured MHRA-approval for clinical research with DyNeuMo in the MINDS trial at Oxford, and will leverage that dossier for the LGS study. |
| Collaborator Contribution | My partners are supporting the clinical plan of research: In this initial pilot clinical trial, four children with LGS (from the largest paediatric epilepsy surgery network in the UK) will be implanted with CMN DBS. To facilitate meeting the aims of this research, we have broken the plan into 4 work packages: WP 1 - Regulatory preparation (month 0-2): This work package will start with setting up a DBS system including generation of the protocol and the design dossier (clinical evidence report, device design and testing files, manufacturing) for an MHRA device-trial. Ethical approval from an NHS Research Ethics Committee (REC) will be obtained before starting recruitment. This work draws heavily from our MHRA-approved MINDS trial, and ongoing collaborations with Bioinduction. WP2 - Clinical Component (month 2-12): four patients from KCH and GOSH studied will be selected for CMN DBS. Only patients with at least 10 seizures per month in the pre-implantation period will be included in the study. All patients will undergo the following prospective study design: * Baseline period (3 months): A three-month period pre-implantation to assess history, general and neurological examination, seizure diary, ECG, EEG, neuroimaging, and patient related outcome measures (PROMs). * Post-implant recovery period (no-stimulation, 1 month): Stimulation will be turned off to study the insertion effect of the leads * Stimulation period (6 months): throughout this stage, all patients will have stimulation activated and the impact of stimulation on seizure frequency and severity assessed. WP 3 - Assessment of DBS and analysis of data (month 9-12): Seizure frequency and severity will be used to assess the effects of DBS implantation. To determine whether the numbers of clinical seizures and epileptiform discharges have been significantly reduced, a manual and an automatic analysis of interictal and ictal events before and after DBS implantation will be performed, including use of the novel physiology toolkit in the DyNeuMo. Statistical analysis will compare the number of clinical seizures, subclinical seizures and interictal discharges between pre and post DBS stimulation periods. WP 4 - Prepare for follow-on study (month 12): We will disseminate results (no restrictions), and use this pilot data to apply for a multi-centre pivotal trial grant (e.g. i4i/NIHR). |
| Impact | We have secured £53000 in direct funding based on our collaboration to start a pilot trial in Lennox-Gastaut epilepsy. This involves clinical partners, neuroscience and engineering. In 2021, we secured an additional £415,000 from LifeArc for a 22 patient clinical study. |
| Start Year | 2020 |
| Description | Morpheus - exploring sleep with medical implants |
| Organisation | Mayo Clinic |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | The collaboration aims to characterize sleep physiology in brain networks, including an assessment of observability and controllability of sleep dynamics through sensing and targeted stimulation. The insight gained from this characterization will be used to explore closed-loop algorithms for real-time enhancement and control of sleep and alertness. The outcome will be a proof-of-concept neural system for management and optimization of sleep using deterministic data-driven principles, including a framework for studying sleep perturbations and how they might inform adaptive modulation in the future. These insights will inform strategies for assisting a patient in optimizing their sleep needs, sleep & wake transitions, or assisting the injured patient with traumatic brain injury (TBI) in recovery of lost sleep function. Sleep is also a co-morbidity for many neurological disorders, and the enhancement of sleep with targeted neurotechnology could have wide ramifications. Oxford is the principal investigator on this sleep programme. |
| Collaborator Contribution | UCSF is providing clinical data from their in-human Parkinson's implants. Mayo is providing clinical data from their in-human epilepsy implants. Surrey is supporting Oxford with clinical testing at the Surrey Sleep Centre. |
| Impact | Publication (Review) summarizing sleep effects in Parkinson's disease accepted by Movement Disorders. |
| Start Year | 2020 |
| Description | Morpheus - exploring sleep with medical implants |
| Organisation | University of California, San Francisco |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | The collaboration aims to characterize sleep physiology in brain networks, including an assessment of observability and controllability of sleep dynamics through sensing and targeted stimulation. The insight gained from this characterization will be used to explore closed-loop algorithms for real-time enhancement and control of sleep and alertness. The outcome will be a proof-of-concept neural system for management and optimization of sleep using deterministic data-driven principles, including a framework for studying sleep perturbations and how they might inform adaptive modulation in the future. These insights will inform strategies for assisting a patient in optimizing their sleep needs, sleep & wake transitions, or assisting the injured patient with traumatic brain injury (TBI) in recovery of lost sleep function. Sleep is also a co-morbidity for many neurological disorders, and the enhancement of sleep with targeted neurotechnology could have wide ramifications. Oxford is the principal investigator on this sleep programme. |
| Collaborator Contribution | UCSF is providing clinical data from their in-human Parkinson's implants. Mayo is providing clinical data from their in-human epilepsy implants. Surrey is supporting Oxford with clinical testing at the Surrey Sleep Centre. |
| Impact | Publication (Review) summarizing sleep effects in Parkinson's disease accepted by Movement Disorders. |
| Start Year | 2020 |
| Description | Morpheus - exploring sleep with medical implants |
| Organisation | University of Surrey |
| Department | Surrey Sleep Research Centre |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | The collaboration aims to characterize sleep physiology in brain networks, including an assessment of observability and controllability of sleep dynamics through sensing and targeted stimulation. The insight gained from this characterization will be used to explore closed-loop algorithms for real-time enhancement and control of sleep and alertness. The outcome will be a proof-of-concept neural system for management and optimization of sleep using deterministic data-driven principles, including a framework for studying sleep perturbations and how they might inform adaptive modulation in the future. These insights will inform strategies for assisting a patient in optimizing their sleep needs, sleep & wake transitions, or assisting the injured patient with traumatic brain injury (TBI) in recovery of lost sleep function. Sleep is also a co-morbidity for many neurological disorders, and the enhancement of sleep with targeted neurotechnology could have wide ramifications. Oxford is the principal investigator on this sleep programme. |
| Collaborator Contribution | UCSF is providing clinical data from their in-human Parkinson's implants. Mayo is providing clinical data from their in-human epilepsy implants. Surrey is supporting Oxford with clinical testing at the Surrey Sleep Centre. |
| Impact | Publication (Review) summarizing sleep effects in Parkinson's disease accepted by Movement Disorders. |
| Start Year | 2020 |
| Description | OpenMind Consortium |
| Organisation | Brown University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | The "Open Mind" neural communications consortium was formed to accelerate cooperation and innovation in the use of implantable neurostimulation hardware platforms. These next generation devices incorporate sensing of cortical and subcortical field potential activity, with the capability for wireless streaming from the internal device to external computers over years. Our founding team represents the major clinical areas of interest in neuromodulation: movement disorders (UCSF), epilepsy (Mayo Clinic), and psychiatry (Brown/Baylor), and includes experts in the design and dissemination of implantable devices (Oxford), and in neuroethics. This consortium will facilitate already funded proposals, as well as entry of new investigators, in the rapidly evolving ecosystem of implantable wireless neural interfaces. Our goal is to provide investigators with critical elements to the launch of their own clinical studies: A "turnkey" user interface to get started, a library of more sophisticated, open source software elements for neural sensing at home paired with peripheral monitors, and streamlined regulatory pathway for FDA approval of investigational protocols, which we call the "Open Source Quality Management System". We will disseminate education and resources through biannual workshops and a web-based library of regulatory documents, software, and the Quality Management System*. |
| Collaborator Contribution | See above -- we are part of a broader consortium supporting first-in-human research tools. Oxford focus is on design and regulatory support for new tools. |
| Impact | the partnership includes clinicians, engineers, and regulatory experts. Publications to date in Neuron: https://pubmed.ncbi.nlm.nih.gov/33120024/ and Nature Biotechnology (accepted, BioRxiv link): https://www.biorxiv.org/content/10.1101/2020.02.13.948349v1 The impact for economic and policy is related to our platform distribution model for new first-in-human research tools. |
| Start Year | 2020 |
| Description | OpenMind Consortium |
| Organisation | Mayo Clinic |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | The "Open Mind" neural communications consortium was formed to accelerate cooperation and innovation in the use of implantable neurostimulation hardware platforms. These next generation devices incorporate sensing of cortical and subcortical field potential activity, with the capability for wireless streaming from the internal device to external computers over years. Our founding team represents the major clinical areas of interest in neuromodulation: movement disorders (UCSF), epilepsy (Mayo Clinic), and psychiatry (Brown/Baylor), and includes experts in the design and dissemination of implantable devices (Oxford), and in neuroethics. This consortium will facilitate already funded proposals, as well as entry of new investigators, in the rapidly evolving ecosystem of implantable wireless neural interfaces. Our goal is to provide investigators with critical elements to the launch of their own clinical studies: A "turnkey" user interface to get started, a library of more sophisticated, open source software elements for neural sensing at home paired with peripheral monitors, and streamlined regulatory pathway for FDA approval of investigational protocols, which we call the "Open Source Quality Management System". We will disseminate education and resources through biannual workshops and a web-based library of regulatory documents, software, and the Quality Management System*. |
| Collaborator Contribution | See above -- we are part of a broader consortium supporting first-in-human research tools. Oxford focus is on design and regulatory support for new tools. |
| Impact | the partnership includes clinicians, engineers, and regulatory experts. Publications to date in Neuron: https://pubmed.ncbi.nlm.nih.gov/33120024/ and Nature Biotechnology (accepted, BioRxiv link): https://www.biorxiv.org/content/10.1101/2020.02.13.948349v1 The impact for economic and policy is related to our platform distribution model for new first-in-human research tools. |
| Start Year | 2020 |
| Description | OpenMind Consortium |
| Organisation | University of California, San Francisco |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | The "Open Mind" neural communications consortium was formed to accelerate cooperation and innovation in the use of implantable neurostimulation hardware platforms. These next generation devices incorporate sensing of cortical and subcortical field potential activity, with the capability for wireless streaming from the internal device to external computers over years. Our founding team represents the major clinical areas of interest in neuromodulation: movement disorders (UCSF), epilepsy (Mayo Clinic), and psychiatry (Brown/Baylor), and includes experts in the design and dissemination of implantable devices (Oxford), and in neuroethics. This consortium will facilitate already funded proposals, as well as entry of new investigators, in the rapidly evolving ecosystem of implantable wireless neural interfaces. Our goal is to provide investigators with critical elements to the launch of their own clinical studies: A "turnkey" user interface to get started, a library of more sophisticated, open source software elements for neural sensing at home paired with peripheral monitors, and streamlined regulatory pathway for FDA approval of investigational protocols, which we call the "Open Source Quality Management System". We will disseminate education and resources through biannual workshops and a web-based library of regulatory documents, software, and the Quality Management System*. |
| Collaborator Contribution | See above -- we are part of a broader consortium supporting first-in-human research tools. Oxford focus is on design and regulatory support for new tools. |
| Impact | the partnership includes clinicians, engineers, and regulatory experts. Publications to date in Neuron: https://pubmed.ncbi.nlm.nih.gov/33120024/ and Nature Biotechnology (accepted, BioRxiv link): https://www.biorxiv.org/content/10.1101/2020.02.13.948349v1 The impact for economic and policy is related to our platform distribution model for new first-in-human research tools. |
| Start Year | 2020 |
| Description | xTMS collaboration |
| Organisation | The Magstim Company Limited |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | The economic cost of neurological disorders exceeds £100B/yr in the UK alone, and new technologies that might provide therapeutic solutions are increasingly attractive. This project will deliver a versatile scientific instrument for non-invasive actuation of the nervous system using Transcranial Magnetic Stimulation (TMS). The new system, MAGNETO, closes key performance gaps in stimulation capability that enables new therapeutic potential for neurological disorders. We have already secured lead clinical users at Oxford, King's College, UCL and Cambridge to apply the tool to explore novel therapies for high-need areas in stroke, epilepsy, motor systems and neuropsychiatry (depression, anxiety), respectively. Their insights will guide the design process and maximise translation probability. With the guidance of these lead-users, MAGNETO will enable: 1) the ability to prescribe novel patterns of stimulation enabled with our unique technology, 2) the modelling of the magnetic coupling to the neural interface for exploring optimal pulse parameters, and 3) real-time control capability for automated exploration of pulse shape and patterns. The key deliverable will be a fully-integrated prototype medical device suitable for first-in-human studies. The expectation is that these studies focus on the clinical translation of therapies for major neurological disorders. |
| Collaborator Contribution | Magstim has provided direct funds for the transistors and power electronic assemblies for the prototypes to support Oxford, Cambridge and King's. For in-kind, they have provided TMS coils and electronics, design guidance, regulatory guidance, and human factors feedback throughout the project. |
| Impact | Publications are noted in the publications tab. Our outcome for the xTMS tool is noted in the research platforms/instrumentation support tab. |
| Start Year | 2020 |
| Title | EMULATION OF ELECTROPHYSIOLOGICAL SIGNALS DERIVED BY STIMULATION OF A BODY |
| Description | An emulation apparatus emulates an electrophysiological signal derived from a target area of a human or animal nervous system under the influence of a stimulation signal applied to the human or animal body. A prior signal generator generates a prior signal representing an electrophysiological signal in the absence of stimulation. A test signal representing a stimulation signal is received and used by a modelling unit to derive a modulation signal representing the degree of modulation of the electrophysiological signal, in accordance with a model of the temporal evolution of the modulation of the electrophysiological signal caused by the stimulation signal. A modulation unit modulates the prior signal in accordance with the modulation signal to output an emulation signal representing an electrophysiological signal derived under the influence of the stimulation signal. The emulation apparatus has wide use in neuroscience research, bioengineering and clinical applications. |
| IP Reference | US2022143415 |
| Protection | Patent / Patent application |
| Year Protection Granted | 2022 |
| Licensed | No |
| Impact | We are beginning to engage with licensing offices at major companies through Oxford University Innovations. |
| Title | GENERATION OF CONTROLLABLE MAGNETIC STIMULI |
| Description | This is a patent on the control of magnetic stimuli for transcranial magnetic stimulators. |
| IP Reference | EP4114515 |
| Protection | Patent / Patent application |
| Year Protection Granted | 2023 |
| Licensed | Yes |
| Impact | The intellectual property was licensed to Magstim Ltd. in Whitland Wales |
| Title | Picostim-DyNeuMo: Dynamic Neuro Modulator for Incontinence with Spin-out (Amber) |
| Description | This is the use of the Picostim DyNeuMo for treating mixed urinary incontinence. The trial has implanted 5 subjects and will finish enrolment in early 2023. |
| Type | Therapeutic Intervention - Medical Devices |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2022 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | Clinical trial results being compiled for a Series A financing round. |
| URL | https://www.ox.ac.uk/news/2023-01-31-oxford-spinout-trials-revolutionary-bioelectronic-implant-treat... |
| Title | Picostim-DyNeuMo: Dynamic Neuro Modulator for Lennox Gastaut Epilepsy |
| Description | This is another application of the Picostim DyNeuMo research tool focused on pediatric epilepsy. |
| Type | Therapeutic Intervention - Medical Devices |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2022 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| UKCRN/ISCTN Identifier | NCT05437393 |
| Impact | We have secured additional funding for a follow-on trial, and are in stage 2 of an i4i grant to develop an more advanced adaptive stimulation methodology. |
| Title | Picostim-DyNeuMo: Dynamic Neuro Modulator for Multiple System Atrophy |
| Description | Neurological disorders create an annual economic burden of over £100B in the UK alone[1], and this cost does not fully capture the personal impact of disease. To help address this burden, roughly 100,000 neural implants per year are currently placed worldwide in patients for prosthesis, movement disorders, epilepsy, chronic pain and incontinence. These systems provide unique access to the nervous system in humans suffering from disease. Despite this opportunity, the ability to perform translational clinical neuroscience and develop improved therapies for patients is not fully leveraged due to limitations with existing devices, healthcare economics, and business models. The Picostim-DyNeuMo ("dynamo") research system aims to catalyse new solutions to this healthcare challenge. The Picostim-DyNeuMo system is a new neuroscience platform that facilitates translational research in neurological and neurodegenerative disorders. Picostim-DyNeuMo uses a state-of-the-art neural implant that leverages routine clinical procedures. While supporting existing "brain pacemaker-based" treatments, the system's upgraded instrumentation capability enables novel research into disease mechanisms and exploration of improved treatments: • Precise, chronic (24/7) access to brain networks in real-world environments will provide insights into circadian rhythms, sleep, and long-term disease progression; • The ability to deterministically probe brain networks with stimulation and pharmacological interventions will help elucidate mechanisms of action; • The modularity of the system platform, and ability to iteratively prototype, enables a flexible and interactive approach to developing therapies and testing new algorithm controls, and a fast track to commercialising successful interventions. Picostim-DyNeuMo has an operational implantable system prototype, first-in-man regulatory approval for studies in the UK, and will support researchers will a fully-completed master file for IDE submission to the MHRA. |
| Type | Therapeutic Intervention - Medical Devices |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2020 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| UKCRN/ISCTN Identifier | https://www.clinicaltrials.gov/ct2/show/NCT05197816 |
| Impact | From a research perspective, the system design and collaborative model addresses multiple concerns with existing tools through careful system design: • Artefacts: the cranially mounting avoids the ECG (electrocardiographic) and motion disturbances that are common in chest-mounted, and neck-tunnelled systems. The patient also benefits from avoidance of bow-stringing and residual tunnelling and chest pain, the most common complaint with existing brain stimulation systems. • Longevity: the rechargeable system lasts through more than a thousand cycles with modest capacity fade, enabling up to a decade of research and long-term subject support. • Flexibility: the rechargeable battery technology provides access to state-of-the-art electronics. Embedded algorithms for adaptive stimulation delivery are fully customized for protocols through a wireless firmware upgrade process. As ideas evolve, the software is upgradeable through wireless telemetry. The stimulation pattern generator enables advanced settings such as expanded frequency range, burst patterns, and an automated circadian scheduler. • Convenient for the research subject: the subject receives their stimulation therapy, with confidence in a long-term implant support. The hand-held communicator also manages recharge - there is only one peripheral device to manage. The embedded battery means that the system is fully hidden from view; there is no wearable energy and algorithm device required to benefit from the implant. • Convenient for the researcher: the customized research tools are delivered as a fully tested and complete system, which reduces regulatory burden for investigators. The design history files and test reports are provided to the regulators in a master file, and supported by the Picostim-DyNeuMo team, to ensure a smooth IDE process. |
| Title | xTMS - research system for flexible transcranial magnetic stimulation |
| Description | The total economic cost of neurological disorders exceeds £100B/yr in the UK alone. New neurotechnologies that might provide therapeutic solutions are increasingly attractive as pharma pulls back investment. MAGNETO will deliver a versatile scientific instrument for non-invasive actuation of the nervous system using Transcranial Magnetic Stimulation (TMS). We will develop an integrated solution to stimulate and sense neural circuits. The project integrates four cross-disciplinary work-packages: 1) Applying state-of-the art power semiconductors and machine technology to deliver a step-change in the capability of the electronic systems that drive TMS coils. 2) Developing high-fidelity biophysical models to guide and interpret the actuation of the nervous system, so researchers can fully leverage the new electronic capability. 3) Implementing a real-time controller that links the model predications with pulse pattern generation in the TMS system. 4) Integrating these work packages into a fully-functional instrument that enables novel studies in humans. |
| Type | Support Tool - For Fundamental Research |
| Current Stage Of Development | Refinement. Clinical |
| Year Development Stage Completed | 2021 |
| Development Status | Under active development/distribution |
| Impact | We have already secured lead clinical users at Oxford, King's College, UCL and Cambridge to apply the tool to explore next-generation therapies in rehabilitation, epilepsy, motor systems and neuropsychiatry (depression, anxiety), respectively. We have completed pilot prototypes of each work-package; this grant will translate these prototypes into a production-intent clinical system. IP is filed on the critical circuit technology via OUI. We are interested in collaborating with manufacturers of TMS systems to provide a direct pathway to clinical impact at a global scale. Matching funds from MRC iCase studentships and the Brain Network Dynamic Unit help to offset the development costs for partners. |
| Company Name | AMBER THERAPEUTICS LTD |
| Description | Urinary incontinence (UI) is a common condition that can severely impact physical, mental and financial wellbeing. Though it is thought at least 8.5% of the global population suffer from UI, many do not admit it, with fewer than half of adults with severe UI seeking help from healthcare providers; one study found that men would rather admit to sexual impotence than symptoms of incontinence. Amber-UI will be a highly innovative implantable bioelectronic neuroprosthesis intended to provide synthetic continence reflexes in patients with UI who have not responded to simple treatments like lifestyle changes, pelvic floor exercises, medication, bladder injections, etc. Where current options for these patients consist of high-risk, variably successful surgery or dated one-size-fits-all electrical stimulation therapies that mostly only reduce rather than cure symptoms, Amber-UI will bring intelligent adaptive stimulation. It will respond to the individual patient's physiology and measurable biomarkers of both 'urge' (the sudden need to urinate) and 'stress' events (coughing, sneezing, lifting, etc). In effect, Amber-UI will restore the normal mechanisms of continence in a large group of UI patients so that they remain dry all the time-transforming these patients' lives. Conducting experimental medicine in first-time-in-human studies, this project will refine Amber-UI's minimally-invasive surgical technique so that it requires a similar surgeon skill/time commitment as current electrical stimulation therapy surgeries, and it will explore and optimise Amber-UI sensing and stimulation to ultimately provide patients with synthetic reflex control of continence. |
| Year Established | 2020 |
| Impact | We have won a £1.1M Biomedical Catalyst grant and secured an additional £1M of venture capital investment for our seed round. |
| Website | https://www.amber-tx.com/ |
| Description | In Control by Design -- Patient Outreach and Group Workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | 'In Control By Design' was a novel kind of collaborative effort that brought together people living with Parkinson's disease, researchers at Oxford University's MRC Brain Network Dynamics Unit and the Pitt Rivers Museum. The project aimed at exploring object design as well as technological solutions that could be helpful in coping with some of the everyday challenges Parkinson's. Meetings made use of the museum's collection of comparative technology to reflect on design solutions from other cultures and time periods, and offered a place for participants to experiment with thematic assortments of contemporary assistive tools. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Introduction to Bioelectronic Medicines / School Talks |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | I have given this talk to schools in the community - with Zoom, this includes parents and siblings many times. The latest example is from Radley College, where over 125 students and parents were in attendance. I offer this as a resource to the local community for science classes. abstract of the talk: Cochlear implants and heart pacemakers have drastically improved the lives of many people with long-term health conditions. This interactive presentation looks at implantable medical devices and the engineering behind them as digital technologies and miniaturisation promise to deliver new therapies and help us to understand how the nervous system works. We also discuss the opportunities and ethical challenges surrounding human augmentation, and what students might need to consider in their own futures. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://twitter.com/RadleyCollege/status/1349826604055359500 |