Walking speed improvements

Walking improvement can be achieved with fampridine, which is a slow release formulation of an old drug called 4-aminopyridine. 

Here, we have a slow release of a different old drug (amantadine) to also improve walking speeds.

Cohen JA, Hunter SF, Brown TR, Gudesblatt M, Thrower BW, Llorens L, Souza-Prien CJ, Ruby AE, Chernoff DN, Patni R. Safety and efficacy of ADS-5102 (amantadine) extended release capsules to improve walking in multiple sclerosis: A randomized, placebo-controlled, phase 2 trial. Mult Scler. 2018 Jan 1:1352458518754716. doi: 10.1177/1352458518754716. [Epub ahead of print]

BACKGROUND:Walking impairment causes disability and reduced quality of life in patients with multiple sclerosis (MS).
OBJECTIVE:Characterize the safety and efficacy of ADS-5102 (amantadine) extended release capsules, 274 mg administered once daily at bedtime in patients with MS with walking impairment.
METHODS:This randomized, double-blind, placebo-controlled, 4-week study was conducted at 14 trial sites in the United States. Study objectives included safety and tolerability of ADS-5102, and efficacy assessments (Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), 2-Minute Walk Test, and Multiple Sclerosis Walking Scale-12). Fatigue, depression, and cognition also were assessed.
RESULTS:A total of 60 patients were randomized (30 to ADS-5102 and 30 to placebo); 59 of whom were treated. The most frequent adverse events (AEs) were dry mouth, constipation, and insomnia. Five ADS-5102 patients and no placebo patients discontinued treatment due to AEs. One patient in the ADS-5102 group experienced a serious AE-suspected serotonin syndrome. A 16.6% placebo-adjusted improvement was seen in the T25FW test ( p < 0.05). A 10% placebo-adjusted improvement in TUG was also observed. No changes in fatigue, depression, or cognition were observed.
CONCLUSION:ADS-5102 was generally well tolerated. These data demonstrate an effect of ADS-5102 on walking speed. Further studies are warranted to confirm these observations.

Some money is been made on fampridine, which improves walking speed in some people,. This suggests that there is some money to be had in symptom control. Therefore some companies are still willing to invest in drug development for symptoms.

ADS-5102, a high-dose amantadine agent taken once-daily at bedtime is designed to provide a slow initial rate-of-rise in drug concentrations and a delayed time to the maximum concentration.

Amantadine is used to treat Parkinson's disease, notabably the extended release formulation is used to treat dyskinesia, a side effect of levodopa which is taken by people who have Parkinsons. Amantadine has some antiviral activity but its use for symptom control are due to its action as a weak antagonist of the NMDA-type glutamate receptor, increases dopamine release, and blocks dopamine reuptake (meaning there is more dopamine available to nerves).

The drug has many effects in the brain, including release of dopamine and norepinephrine from nerve endings. It is also anticholinergic (blocks nerves using acetyl choline as a neurotransmitter and notably in this case it is a nicotinic alpha-7 antagonist like the similar pharmaceutical memantine, which is used to slow memory loss in Alzheimers disease and is neuroprotective in animals.

However, this is a problem too, because anti-cholingeric drugs cause dry mouth and constipation and sleep issues and are probably the cause of the side-effects in this study.

How many of you take symptom-control drugs, and what side-effects do you put up with to experience an improvement in those symptoms?