The primary aim of this study is to discover whether patients with CMT type 1 and 2 have neuromuscular junction transmission deficits.

The secondary aim is to collect information of different clinical and electrophysiological test procedures to perform possible future clinical trials in CMT patients.

The study is a prospective observational pilot study involving two investigational sites:

1. Department of Neurology, Arhus University Hospital
2. Department of Neurology, Ohio State University

A total of 20 patients with Charcot-Marie-Tooth (CMT) disease and 10 healthy age-matched controls will be included with each site including 10 CMT patients and 5 Healthy Controls. CMT patients will undergo electrophysiological (repetitive nerve stimulation and single fiber EMG analyses) and functional (different tests of muscle strength, fatigability, dexterity, and balance) testing on 4 separate occasions. Healthy controls will undergo electrophysiological testing at baseline only.

To assess whether patients with CMT have deficits in NMJ transmission, results from repetitive nerve stimulation and single fiber EMG analyses in CMT patients will be compared to those obtained in healthy controls at baseline. To inform future clinical trials, results relability and tolerability estimates obtained from sequential electrophysiological and functional tests will be calculated

Inclusion Criteria for CMT Patients

• Age ≥ 18 years
• Diagnosis of CMT confirmed by:
• Clinical presentation and electro diagnostics or genetics
• Physical Features (all must apply): 1) Ambulation for at least 10 meters, without a brace 2) Left and right ankle plantar flexion Medical Research Council (MRC) grade 2 to 5, inclusive 3) Left and right ankle dorsiflexion MRC manual muscle testing (MMT) grade 2 to 4+, inclusive.
• Ability to adhere to the study visit schedule/procedures, and to understand and comply with protocol requirements
• Stable concomitant medications for 2 months prior to enrolment
• Signed written informed consent

Exclusion Criteria for CMT Patients

• Severe deformity or ankle contracture that would sufficiently limit passive range of motion to affect assessment of dorsiflexion strength
• Ulceration that would interfere with functional ability
• Recent major surgery
• Significant change in physical activity or exercise (e.g., significant increase or decrease in intensity or frequency) within 8 weeks before Study Day 1 or inability to maintain the baseline level of physical activity throughout the study
• Any disability or condition that would prevent completion of the study tasks
• Moderate to severe Neuropathic or inflammatory/musculoskeletal pain that would interfere with performance of the tests
• A diagnosis of a primary NMJ disorder such as myasthenia gravis, Lambert Eaton Myasthenic Syndrome or congenital myasthenic disorder

Inclusion Criteria for Healthy Volunteers

• Healthy male or female volunteers
• Age ≥18 years
• Able to give written informed consent

Exclusion Criteria for Healthy Volunteers

• Pregnant
• Requiring prescription medicines likely to interfere with electromyography (EMG) recordings
• Presence of current or previous medical condition which might interfere with participation in the study

Eligible CMT patients will be invited to participate at the respective study sites. Age matched healthy volunteers will be recruited through advertisement at the respective study sites