Sunday, 4 February 2018

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?

13 comments:

  1. I read that amantadine can help control some seizures but also increase seizure activity, what one is correct or is it both? thanks

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    1. I don't know but seizures can be occur do to loss of function in some intances and gain of function in other instances so could be both

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  2. how about amphetamine? it will certainly increase walking *speed*

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  3. beta-ketones also. I heard in this blog that ketones are beneficial in MS. So why we cant use them to threat both the condition and the symptoms ;)

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  4. I take Fampridine. As well as doubling my walking speed from very very very slow to very very slow it has effectively put my MS clock back by about 2 years. As well as being able to stand for longer, stronger legs and better balance I now have more feeling in my finger tips and less clumsiness in arms and legs. Other people have noticed an improvement in bladder control. It has not helped the hyper-extension of my knee.

    The only draw back is not being able to eat 2 hours before taking the pill or for 1 hour afterwards and you have to take it every 12 hours. Seizures can occur but I think it only happens if you don't follow the guidelines.

    It has improved my quality of life as well as my walking speed but despite authorisation NICE will not licence it - such a shame.

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    1. Bet you haven't been taking it long. It did magical things for me when I first took it but then I started to deteriorate faster than I ever had. And faster than friends who'd tried fampridine and had intolerable side effects. MS is a long term disease and there should be consideration of what drugs do in the medium to long term.

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    2. Interesting we wanted to examine this. Company didn't want to know the answer

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    3. Coordelia, The same drug can affect each person in different ways. My MS is probably very different from yours. I have heard stories ranging from 'Do not touch it, it nearly killed me' to 'It is fantastic, I can now do so much' Who do you believe? So far it works for me.

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  5. Fampyra doesn't help everyone I happen to be a "responder" and paid for it (nearly €300 per month) myself for a while. Following a long campaign, we got the HSE to fund it, but only for responders.So you do a timed walk, get it for a month, then get timed again. Which is ok, except the forms and other paperwork are extremely time consuming for any neuro and will mean those in the public system may end up losing out as a result. And the timed walk doesn't take MS progression into account. For me, Fampyra has meant greater stamina and less pain, who cares about speed!

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