Exploration of TMS as a potential early biomarker for ALS
Research type
Research Study
Full title
Exploration of transcranial magnetic stimulation(TMS) as a potential early biomarker for amyotrophic lateral sclerosis (ALS) and application to novel drug discovery.
IRAS ID
278835
Contact name
Chris Shaw
Contact email
Sponsor organisation
Director of Research Management & Director of Administration (Health Schools),KCL
Duration of Study in the UK
2 years, 8 months, 30 days
Research summary
This study will recruit 30 patients from KCH Motor Nerve Clinics, comprising a mixture of patients with Amyotrophic Lateral Sclerosis (ALS)and ALS mimics (Kennedy’s Disease and Multifocal Motor Neuropathy) in a 12-month longitudinal study.
ALS is a neurodegenerative disorder characterised by degeneration of both upper (UMN) and lower (LMN) motor neurons, resulting in progressive muscle wasting , paralysis and death from respiratory failure on average within three year of symptom onset. There are currently no effective therapies and the discovery of novel therapies is significantly held back by the lack of early diagnostic and disease progression biomarkers.
There is growing evidence that both cortical (UMN) and spinal (LMN) hyperexcitability occur upstream to motor neuron degeneration in ALS. Muscle fasciculations represent the hyperexcitability of LMNs and can be objectively confirmed by high-density surface electromyography (HDSEMG). In contrast, the lack of an objective marker of UMN hyperexcitability contributes to the long diagnostic delay most patients experience (a year on average). Over the last three decades, TMS has been combined with EMG and electroencephalography (EEG) to non-invasively assess cortico-spinal and cortical excitability in other neurological diseases.
We predict that abnormalities of spinal(HDSEMG), cortico-spinal (HD-TMS) and cortical (TMS-EEG) excitability parameters can be used to quantify hyperexcitability as an early diagnostic and serial biomarker in ALS patients.
We will compare these measurements in ALS versus ALS mimics patients as they only have modesty reduced lifespans and no cortical involvement, despite an initially similar clinical manifestation, and therefore represent an optimal control group to identify an objective marker of UMN hyperexcitability in ALS. At each visit, we will take resting HDSEMG from a small muscle on the back of the hand and perform HD-TMS and TMS-EEG. We will also perform standard clinical measures of disease progression and collect blood samples for serum measurements of a validated fluid diagnostic biomarker of ALS.REC name
London - Fulham Research Ethics Committee
REC reference
21/PR/0272
Date of REC Opinion
11 May 2021
REC opinion
Further Information Favourable Opinion