Exploration of TMS as a potential early biomarker for ALS and application to novel drug discovery

Primary Hypothesis: Abnormalities of peripheral (HDSEMG), cortico-spinal (TMS-EMG) and cortical (TMS-EEG) excitability parameters can be used to quantify the cortical hyperexcitability state as a subclinical serial biomarker of motor neuron degeneration and could also reflect a response to therapeutic intervention as they are potentially linked to pathological molecular processes in ALS.

1. Could the combination of HDEMG and TMS-EDM provide output measures to identify early deficits in ALS patients? In a longitudinal study, we aim to validate the use of previously reported neurophysiological parameters as diagnostic biomarkers of subclinical cortical hyperexcitability in ALS.

2. Could the most sensitive output measures established from the longitudinal study be used for patient selection and early clinical testing of novel Kv3 modulators? In an early pilot study, we aim to use our most sensitive neurophysiological biomarkers as therapeutic efficacy biomarkers to confirm and explore target engagement and pharmacodynamics effect of novel Kv3/Kv7 modulators developed by Autifony.