Patients with motor neurone disease typically experience relentless motor decline and die within three years of symptom onset from respiratory muscle weakness. There are currently no effective therapies and the discovery of novel therapies is hampered by the lack of a sensitive disease biomarker. Consequently, there is a huge drive to discover novel biomarkers, which can reliably track disease progression over time. These can then be incorporated into clinical drug trials to expedite effective drug discovery.

Muscle fasciculations represent the hyperexcitability of diseased motor neurons and are almost universally present from the early stages of MND. We predict that the site, frequency and shape of fasciculations might provide a sensitive measure of disease progression in an individual.

We have been conducting a 12-month longitudinal study of 25 patients, performing high-density surface EMG every two months. We have validated an automated technique to process these large data sets. Ultrasound is widely used in clinical medicine to assess anatomical structure in a safe and non-invasive way. Dr Emma Hodson-Tole (Manchester Metropolitan University) and her group have been applying this to the analysis of fasciculations in healthy individuals and patients with MND.

This collaborative project will explore combining these two techniques simultaneously in patients with motor neuron disease and control subjects. The goal is to explore the nature of electro-mechanical coupling related to fasciculations and to determine whether any of these properties are pathophysiological. This would complement other studies from our two groups, investigating the natural history and potential utility of fasciculations as a biomarker of motor neuron health in MND.

Inclusion criteria for MND patients:

(i) Aged between 40 and 80 years of age inclusive, at the time of signing the informed consent.

(ii) Diagnosed with MND by a neurologist with expertise in MND. For subjects with bulbar onset there must be objective limb involvement of at least one limb. (iii) Diagnosed with MND within 24 months of symptom onset. (iv) Subjects must be ambulatory (i.e. must not be confined to a wheelchair). (v) Male and female subjects (vi) Capable of giving signed (or verbal consent or assent where applicable) informed consent as described in Protocol Section 9.2 which includes compliance with the requirements and restrictions listed in the consent form and in the protocol. (vii) Capable and willing to comply with the requirements of the protocol (either by themselves or with assistance).

Inclusion criteria for healthy controls (i) Aged between 40 and 80 years of age inclusive, at the time of signing the informed consent.

(ii) Male and female subjects (vi) Capable of giving signed (or verbal consent or assent where applicable) informed consent as described in Protocol Section 9.2 which includes compliance with the requirements and restrictions listed in the consent form and in the protocol. (vii) Capable and willing to comply with the requirements of the protocol

Exclusion criteria for MND patients:

(i) Neurological (other than the subject's MND) or non neurological co morbidities (e.g. joint disease, respiratory disease) which limit mobility.

(ii) Clinically significant cognitive impairment in the opinion of the investigator or lacking capacity in accordance with the Mental Capacity Act (2005).

(iii) Regionally restricted forms of MND, or other atypical variants:

• Isolated corticobulbar pattern of MND with normal ambulation

• Primary lateral sclerosis

• Signs of chronic partial denervation restricted to a single limb

• MND or parkinsonism dementia complex (iv) Subjects requiring mechanical ventilation (non invasive ventilation for sleep apnoea is allowed).

  (v) Historical or current evidence of clinically significant uncontrolled disease which, in the opinion of the chief investigator, would put the safety of the subject at risk through participation or impact the study assessments or endpoints. (vi) Presence of an active implantable cardiac medical device (e.g., pacemaker or implantable cardioverter defibrillator) or at a high risk for needing external defibrillation.

(vii) History of skin hypersensitivity to adhesives. (viii) Current participation in a clinical trial which in the opinion of the chief investigator might impact the objectives of this study.

Exclusion criteria for healthy participants:

(i) Historical or current evidence of clinically significant uncontrolled disease which, in the opinion of the chief investigator, would put the safety of the subject at risk through participation or impact the study assessments or endpoints. (ii) Presence of an active implantable cardiac medical device (e.g., pacemaker or implantable cardioverter defibrillator) or at a high risk for needing external defibrillation.

(iii) History of skin hypersensitivity to adhesives. (iv) Current participation in a clinical trial which in the opinion of the chief investigator might impact the objectives of this study.