JAMA Neurol: Ezogabine's effect on the excitability of motor neurons in the cortical and spinal cords of ALS patients

Amyotrophic lateral sclerosis (ALS) is a degenerative disease of the motor nervous system.
Through transcranial magnetic stimulation and threshold tracking of nerve conduction studies, the excitability of motor neurons in the cortical and spinal cords in ALS patients was demonstrated to be high, although the excitability indicator has not yet been used as a biomarker for pharmacoetics in clinical trials.
Ezogabine, an auxiliary treatment for local seizures in adult patients with epilepsy, recently examined the effects of Ezogabine on the excitability of motor neurons in the cortology and spinal cord in patients with ALS.
the study was conducted in a double-blind, placebo-controlled Phase II randomized clinical trial at 12 ALS centers in the northeastern United States.
participants were randomly received high doses (900 mg/day) or low doses (600 mg/day) of Ezogabine or placebo for a period of 10 weeks.
and complete clinical assessments and neurophysiological measurements in screening, baseline examination, weeks 6 and 8.
The main results of the
study were short-term intracelial inhibition changes (SICI; SICI-1 to reflect inhibition), and secondary results included cortical motor neuron excitability levels (including resting motion thresholds) measured by cranial magnetic stimulation and spinal motor neuron excitability (including strength-time constants) measured by the threshold tracking neurotransferration study.
65 ALS patients were studied, including 23 in the placebo group, 23 in the 600 mg/day Eezogabine group, 19 in the 900 mg/day Ezogabine group, and 45 men (69.2%) of the participants, with an average age of 58.3 years.
SICI-1 increased by 53% (average ratio 1.53) in patients in the 900 mg/day Ezogabine group compared to the placebo group, while there was no change in the 600 mg/day group SICI-1 (average ratio 1.15).
the 600 mg/day Ezogabine group increased the resting exercise threshold (average ratio 4.61) compared to the placebo group, but there was no significant change in the 900 mg/day Ezogabine group (average ratio 1.95).
intensity-period time constant results showed that the 900 mg/day Ezogabine group led to a decrease in excitability showing dose dependence.
study found that Ezogabine reduced the excitability of motor neurons in the cortical and spinal cords of ALS patients, suggesting that this neurophysiological indicator could serve as a marker for drug physics in clinical trials.
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