#ThinkHand & #ResearchSpeak: are you an irredeemable?

What is it going to take to convince the MS community that arm and hand function is worth saving? #ThinkHand #ResearchSpeak #MSBlog

Are you an irredeemable? If you are not sure then this post is for you. #ThinkHand #ResearchSpeak #MSBlog

Are we ready for a trial of a DMT in pwMS in wheelchairs with the aim of delaying progression of disability in arm and hand function? I am not sure. 

At recent meetings with so called KOLs (key opinion leaders) a large number of them still feel we need to stick to the EDSS and walking time; the so called tried and tested outcome measures, which have recently worked in the ocrelizumab PPMS and siponimod SPMS trials. Do we therefore give-up on the idea of including wheelchair users in trials, or do we try and get a trial funded? 

As a group we launched our #ThinkHand campaign earlier this year, which includes:
  1. Several hypotheses (therapeutic-lag, length-dependent-axonopathy, asynchronous-progressive-MS and MS-is-one-disease-not-2-or-3-diseases), some of which are well supported by data.
  2. Designed, tested and validated a cardboard 9-HPT for home use.
  3. Done web- and MSologists surveys on the importance of hand function in MS and presented the data at ECTRIMS using a hand-made poster and helium filled balloons (ridiculous and apparently against the rules of scientific engagement). 
  4. Wore poorly-designed #ThinkHand T-shirts (who's stupid idea was this?).
  5. Arranged a 'Burning Debate' at ECTRIMS which DrK won supporting the motion that people in wheelchairs should be included in progressive MS studies.
  6. Manned #ThinkHand stands at ECTRIMS, MS Life and the MS Trust Conferences
  7. We have spoken on countless platforms to promote the #ThinkHand campaign.
  8. Presented data on the robust effect of DMTs on hand-function from several older and more contemporary DMTs (data apparently doesn't speak for itself anymore in this post-truth era).
  9. Lobbied pharma to get their acts together to do trials in more advanced MS focusing on arm and hand function as the primary outcome (they are not keen, I suspect the cost-effectiveness of DMTs plummets once people are in wheelchairs, i.e. payers won't pay a premium for DMTs in this patient group). 
  10. We are also developing a new outcome measure to assess hand function in MS; this is a work in progress and we want it be personalised, or humanised, to reflect what is important to individuals with MS (the community prefers the EDSS and walking times). 
I am feeling very despondent about the #ThinkHand campaign; we don't seem to be any closer to our primary aim of testing a DMT in more advanced MS. At a meeting I attended this weekend one of the senior academics stated that MS is like Alzheimer's and Parkinson's disease, i.e. if wait for people to become progressive, or in the case of AZD and PD develop the disease, before starting DMTs we have missed the boat. We should be treating all pwMS as early as possible to prevent progressive MS. I don't agree with this position, as it is simply writing-off all pwMS  who have more advanced disease as 'irredeemables'. It's like saying 'tough we can do nothing for you, therefore we are going to focus all our attention on people with early MS'.

It is not all bad news if we can't slow down disease progression in your arms then just may be we could offer you a symptomatic treatment to improve hand function? The study below hints at Fampridine being effective on upper limb function. The catch-22 we have in the NHS is that we are not allowed to prescribe the drug, therefore if you have progressive MS and are in a wheelchair then its lose, lose and lose some more. 

We are running out of ideas and need your help. Is there aanyone out there who is prepared to fund a trial of a highly-effective 'off-label' DMT in progressive MS, which will include wheelchair-users? 

Savin et al. Effect of Fampridine-PR (prolonged released 4-aminopyridine) on the manual functions of patients withMultiple Sclerosis. J Neurol Sci. 2016 Jan 15;360:102-9.

BACKGROUND: Persons with MS (PwMS) commonly present ambulatory and manual dysfunctions. While ambulation is recognized as important to PwMS, manual dysfunction is only lately gaining attention. Fampridine-PR was approved for MS ambulatory impairments. Anecdotal evidences indicate possible therapeutic effects on manual function.

OBJECTIVE: To comprehensively assess the effect of Fampridine-PR on manual functions of PwMS.

METHODS: Twenty six PwMS with ambulatory and manual dysfunction assessed before, 1 and 3 months after treatment with Fampridine-PR, applying Timed 25-Foot Walk (T25FW) for ambulation while manual functions were evaluated by several tools addressing the International Classification of Functioning (ICF) concepts. This includes hand grip and pinch strength, 9 Hole Peg Test (9HPT), Arthritis Hand Function Test (AHFT), activities of daily life (ADL) tests, ABILHAND questionnaire and Computerized Penmanship Evaluation Tool (ComPET).

RESULTS: Fampridine-PR increased dominant hand grip and pinch strength 1-month following treatment initiation by 12% and 10% (p<0.05), respectively. 9-HPT improved by 11.3% after 3-months of treatment (p<0.05%) and ABILHAND improved by 16% and 31% (p<0.05%) after 1 and 3-months of treatment. Mean stroke duration in air of the name writing task improved by 21% (p<0.05) following 3-months of treatment. T25FW results were similar to previous reports.

CONCLUSION: The results of this pilot study suggest that Fampridine-PR improves manual function of PwMS. Methods herein indicate that an integrative approach may be useful for evaluation of manual function in MS and in additional neurological diseases.

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