Title: Closed-Loop Electronic Stimulation (ES) - Mechanomyogram Sensor (MMG) System for Passive Tremor Suppression Treatment
Funder: Department of Health and Social Care

Abstract: Background/Need Pathological tremor is the most common movement disorder worldwide, impacting a staggering 5-11% of people over 60 [1]. Treatment options centre on pharmaceuticals and/or surgery; both have limited efficacy and harmful side-effects [2,3] . Furthermore, many patients do not receive appropriate treatment (e.g. 80% of essential tremor patients [3]). Proposed Resolution We introduce a wearable tremor suppression system combining our work in: Low-level Electrical Stimulation (ES): We pioneered the first imperceptible (sub-motor-threshold) ES tremor suppression system. Our clinical testing proved low-level ES suppresses tremor symptomatically [4,5]. Furthermore, we conducted a 9-patient trial [10] showing prolonged tremor reduction using our neuro-stimulation system. Mechanomyography (MMG) closed-loop feedback: We developed [6,7] and patented [9], a novel MMG sensor, the first demonstrated to map muscle activity during tremor [8]. MMG allows closed-loop optimisation of muscle response during ES (impossible with existing EMG). We propose a 24-month program to prototype an 'ES-MMG' wearable tremor treatment system and clinically demonstrate its veracity. Research Questions This program will answer: Is ES-MMG a viable, zero side-effect alternative (even augmentation) to expensive/invasive tremor treatments (pharmacotherapy, botulinum toxin, surgery, etc.)? Does regular ES-MMG tremor treatment reduce the frequency and magnitude of tremor (i.e. produce a patient-specific therapeutic outcome)? Will patients and clinicians comply with use of ES-MMG treatment if packaged as a simple wearable? Aims/Objectives Integration of ES system with closed-loop MMG feedback for sustained tremor suppression Development of patient-specific therapeutic treatment Understanding longitudinal impact of therapeutic treatment to condition and quality-of-life Commercialisation validation, including Independent Health Economic justification Methods/Timelines 24-months, starting 01/03/2021 Prototype Development (12-months): fabricate wearable ES-MMG system 10-Patient Validation Study (1-month): further patient feedback/refinement 20-Patient Longitudinal Study (5-months): placebo-methodology End-to-End Product Refinement/Commercial Validation (6-months): wearable packaging; patient/clinician app development Expected Outcomes 20 patient longitudinal-treatment validation Prototype for subsequent clinical trials Commercial funding secured from feasibility demonstration

Lay abstract: Background Tremor is the most common movement disorder in the world, affecting nearly 1 in 10 people over 60. Numbers in the UK and worldwide are predicted to skyrocket according to population aging projections. Tremor current has no &quot;cure&quot; and a severe quality-of-life impact, making simple activities of living (e.g. eating, dressing, grooming, etc.) difficult or impossible. Furthermore, tremor causes social embarrassment and stigmatization which often determine need for psychological aid. Tremor support in the UK is not proportional to the lifestyle and financial impact on its sufferers. Symptomatic treatment relies on oral medication or neurosurgery. Drug treatment is expensive, minimally effective and provokes side-effects often leading to withdrawal. Neurosurgery is risky, invasive, expensive, and reserved to a minority of patients (3%). Aims We will develop and clinically test a simple wearable armband that senses and suppresses tremor by delivering tiny (unable to be felt) electrical stimulation (ES) to the forearm or wrist. The armband may be worn indefinitely, thus offering the potential for constant tremor suppression. Our team has already developed constituent elements of the system and proven their ability to sense and suppress tremor. This study has the potential to replace and/or augment current tremor treatment, eliminate side-effects, and improve quality-of-life for a very large patient population. Design We will execute a patient-centric design methodology with tight integration of input from clinical, patient, and technical stakeholders. Yr1 will deliver a prototype tremor suppression system with proven functionality, via Concept Trial at St George's Hospital (STGH). Yr2 will extend testing of the refined system (product wrap/economic assessment) via long-term use studies. Groundwork for certification will ensure the system is ready for rapid integration into the NHS. Patient-Public Involvement (PPI) Extensive patient input will be solicited at every stage of design and testing. We will form a patient focus group that will meet at critical program junctures to inform design, direct progress and assess prototypes. We have also secured involvement of two of the largest tremor patient advocacy groups (Parkinson s UK and National Tremor Foundation (NTF) &ndash; see support letters) for steering panels. Dissemination Impact Drivers Our target impact drivers include: Academic: Journal publications (e.g. Neural Engineering) and conference presentations (e.g. IEEE Medicine in Biology) General Public: Press releases (e.g. BBC, ITV as in our past work) industry publications (e.g. The Parkinson Magazine), heavy social media presence (LinkedIn/YouTube (including NHS/Partner channels), public forums(e.g. Imperial College Festival), Clinical: Presentation through our clinical network, presentation at medical conferences Patients: Formation of focus groups for design; dissemination through advocacy groups on our team (Parkinson s UK, NTF) Commercial: Presentation/solicitation of partnerships with commercial partners (e.g. pharmaceutical companies, medical device manufactures) when feasibility is demonstrated; pitches to investors for follow-on trial support

Research activity codes: 5.3 MEDICAL DEVICES;6.3 MEDICAL DEVICES
Health categories: NEUROLOGICAL