Age: 18 - 70+
Healthy Volunteers: Not accepted
Inclusion Criteria:
1. 18-80 years of age inclusive
2. Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported probable, or definite ALS as defined by revised El Escorial criteria
3. Less than or equal to 3 years since ALS symptom onset
4. Slow Vital Capacity ≥ 50% of predicted capacity at the time of Screening as determined using a portable spirometer
5. For TTNCS: Median CMAP ≥ 1.5 mV
6. Willing to forgo botulinum toxin, phenol or alcohol injections, intrathecal baclofen, digitalis, and morphine for the study duration
7. Willing to refrain from participation in any other therapeutic clinical trial or investigational product for ALS for the duration of this study
8. Women must not be able to become pregnant (e.g., post-menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and 3 months after study completion.
9. Stable dose of rilutek (Riluzole), edaravone (Radicava), or tofersen (Qualsody) and oral medications for muscle spasms/cramps (e.g. mexiletine, quinine, quinidine, magnesium, gabapentin, oxcarbazepine, baclofen) for at least 30 days prior to the onset of participation in the study
10. ALS Functional Rating Score (ALSFRS-R) of greater than or equal to 35
11. Willing and able to give informed consent
Exclusion Criteria:
1. Study participants who are on permanent assisted ventilation (PAV) defined as >22h of noninvasive or invasive ventilation a day for > 7 consecutive days.
2. Study participants who have been diagnosed with ALS having only clinical bulbar involvement
3. Implanted intrathecal pump
4. Prior botulinum toxin injection(s) at any site within 12 weeks of study enrollment
5. Prior phenol or alcohol injections for spasticity within 6 months of study enrollment
6. Presence of potential tsDCS and/or TMS risk factors:
1. Damaged skin at the stimulation sites (i.e., skin with ingrown hairs, acne, razor nicks, wounds that have not healed, recent scar tissue, broken skin, etc.)
2. Presence of an electrically, magnetically or mechanically activated implant (including cardiac pacemaker) or any other electrically sensitive support system with the exception of loop recorders
3. Ferromagnetic metal in the head, neck or any site of stimulation including, but not limited to, aneurysm clips, implanted medication pumps, implanted brain stimulators, pacemakers, cochlear implants, implanted metal prostheses or metal due to any injury; dental fillings are permitted. Jewelry must be removed during stimulation
4. Seizures or unexplained spells of loss of consciousness during the previous 12 months
5. Any cardiac abnormality that may be exacerbated by transthoracic electrical stimulation
6. History of cord lesions or previous spinal surgery that may interfere with procedure as determined by the study MD
7. History of intracranial brain lesions, cortical stroke or previous neurosurgery that may interfere with TMS (e.g., in regions to be stimulated for TMS evaluations) as reviewed and approved by the study MD
7. Any medical condition that would prevent the participant from being able to participate in the clinical outcome measures
8. Pregnant females, as determined by a pregnancy test at V1 (in females of child-bearing potential)