Dalfampridine in Parkinson's disease related gait dysfunction: A randomized double blind trial

Abstract

D-ER is well tolerated in PD patients, however it did not show significant benefit for gait impairment.

Potassium homeostasis, oxidative stress, and human disease

“…It influences the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms and pathogenesis of neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, Lou Gehrig’s disease, multiple sclerosis and Parkinson’s disease, as well as atherosclerosis, autism, cancer, heart failure, and myocardial infarction 28,29 . Likewise abnormalities in potassium channel have been reported in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a lethal neurodegenerative disease commonly called Lou Gehrig’s disease 30 , and Parkinson’s disease such that potassium channel blockers are part of treatment regimen in Parkinson’s disease 31 . Enzymes that are involved in OS also affect potassium activities.…”

α-Synuclein–induced Kv4 channelopathy in mouse vagal motoneurons drives nonmotor parkinsonian symptoms

“…Right: Box plot of firing rates demonstrates a slowing of the pacemaker frequency in DMV neurons transfected with AAV-A53T (EV: n = 19 neurons, N = 6 mice; A53T: n = 23 neurons, N = 9 mice; t 40 = 3.32) that is similar to the reduction observed in vivo. Preincubation of the slices in either 1.3 M phrixotoxin-2 (EV: n = 24 neurons, N = 3 mice; A53T: n = 33 neurons, N = 4 mice), a Kv4-selective antagonist or 400 M 4-AP, which, in the submillimolar range, is a selective blocker of A-type Kv currents and which is also approved for clinical use (EV: n = 20 neurons, N = 3 mice; A53T: n = 26 neurons, N = 3 mice)(46,47) occluded the reduction in firing rates (LMEM for initial six-group comparison identified a significant reduction only for the A53T-treated mice with no drugs, t 139 = 4.12, P = 6.6 × 10 −5 ) by significantly elevating the firing rates in A53T-injected mice (phrixotoxin-2: +1.3 spikes/s, t 54 = 3.8; 4-AP: +1.6 spikes/s, t 47 = 3.99; post hoc) relative to the no-drug condition.…”