#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 n ot 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 w e 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. D esigned, 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 a anyone 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.

32 thoughts on “#ThinkHand & #ResearchSpeak: are you an irredeemable?”

  1. Sadly "if you have progressive MS and are in a wheelchair then its lose, lose and lose some more "It seems to be, that if one was labeled with a diagnoses of Primary progressive MS you were indeed left behind and course / decline was of little interest to any medical professional. On a more upbeat tone, I do sense a change of attitude over the last 12 months and maybe that's result of the hard work of this team.Re Fampridine, as I understood it, it improves signals at neuron level ? so why was the primary measure walking speed ? surely if that was the mode of action it could help all aspects of MS ? Or is that too simplistic .Regards as always

  2. "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'."This hits the nail on the head when it comes to some of my fears about both MS research effort and consequently treatments. It is so much easier to brush people off as hopeless cases. And yet the difference between a tremor which "only" makes handwriting difficult, and a tremor which makes it hard to eat is massive, has enormous implications for a person.

  3. We need to relabel MS as a brand of dementia. It is, after all, a form of brain damage. It is a seriously bad disease.No-one takes MS seriously, including pwMS. You have a brain disease. If you downplay it then you won't be taken seriously.

    1. "No-one takes MS seriously, including pwMS." That statement puzzles me. I can't think of anyone I know with MS (myself included) – or anyone who cares about them – who doesn't take it seriously.

  4. Prof G rumour has it, it is your wedding anniversary today. Congratulations. Don't you think you need to take some time off?

    1. Thanks. Yes, it is my 30th, or pearl, anniversary. The decision to work was my wife's she couldn't cancel her work commitments for this week. I also have a grant(s) application to write.

    1. Re: "How advanced does your MS have to be, to be considered an irredeemable?"According to this KoL progressive. In my opinion the progressive phase of the disease is there from the beginning so I don't agree with this line of thought! As far as I am concerned most MSers are redeemable; it is only those that choose to not to be that are irredeemable.

    2. "it is only those that choose to not to be that are irredeemable"Who are you talking about? Who chooses this?

    3. "Who chooses this?" – Anonymous Tuesday, November 15, 2016 2:43:00 pm, is one example. I know of several people with MS who have taken their lives and some who have registered with Dignitas. Not everyone wants to live with a disabling and stigmatizing disease.

    4. Gavin GiovannoniTuesday, November 15, 2016 2:41:00 pmRe: "How advanced does your MS have to be, to be considered an irredeemable?"According to this KoL progressive."What is the KoL's view on when exactly relapsing MS turns progressive in any given individual with MS? Can they tell? Do they disagree? If it's something we can only definitively diagnose retrospectively in most people, then I'm reminded of our furry friends who spend time chasing their own tails.

    5. "As far as I am concerned most MSers are redeemable; it is only those that choose to not to be that are irredeemable "Interesting, encouraging and very useful when trying to persuade otherwise.Thank youRegards as always.

  5. Is it not time for us to protest? We could all wear placards around our necks saying 'irredeemable' and stand outside the entrance of the major MS congresses.

  6. Let's be honest, those of us with advanced MS have had our day. We won't be running, dancing, climbing mountains again. Your proposed trial if it ever takes off will take 10 years plus and NICE will never approve of it. I'd prefer that you focus on the younger folksister. Drugs like Alemtuzumab will greatly reduce damage and a neuroprotective agent must be delivered in the next 5 years. The next generation of Prof G's will focus on neuro restoration (drugs available in 20-25 years). I don't want to sound too cynical but I've lost count of these flurries of activity with nothing being delivered. I gothink too excited by the lamotrogine trial, the stating trial, then the phenotoin trial, then the Charcot trial…anti-lingo trial. We have a graveyard full of failed trial and busted hopes. Forgive me for not getting overexcited with another proposal.

    1. I agree it all sounds like a litany of failures, but that's only true at first sight. Simvastatin may well go into phase III and phenytoin was successful (though I agree there's no plan atm to take this forward/reproduce the result and change practice, which is a shame). Lingo always had a huge mountain to climb being CNS excluded, and instead of Raltegravir we should have chosen a different compound to attack the HERV question. So, it's a mixed bag. The trial we are proposing for advanced MS is not going to take 10 years, but yes 5 years perhaps. Research does take time full stop. However, the landscape of drug licensing is changing, and with an off-label compound NICE wouldn't even bother assessing it, so if there is a positive result, and the drug is safe and affordable, neurologists (and pwMS) should remember they are entitled to make their own judgement, and consider using the compound instead of trying the impossible – submitting for a license. Who knows, once we get some momentum behind this one of the manufacturers might be prepared to chip in.

    2. When people with MS are frustrated at the lack of progress in treating progressive MS, why do neuros get defensive rather then empathise? It's bloody frustrating for people with progressive MS. Not only are they frustrated that there is STILL nothing for them (while the world celebrates the ongoing discussion about how well we are doing with MS because now we can treat it so well!), but they've sat back for years watching the same story hit one progressive trial after another. When they express frustration about this: why go into a song and dance about a mixed bag and upcoming trials (which for most people with long standing MS, EDSS 7.5 and up really does mean very little today)? We all know research takes time, but some people are frustrated because it is 2016 and MS is not a new disease. They have a right to be frustrated, instead of being told they are looking at it all pessimistic-like and, well, research takes time and we'll get there one day.

  7. ProfG, first of all congratulations for your anniversary, wish you all the best for you and your family.I am just a pwMS and not an HCP, but it seems to me that such a trial will be very difficult to be funded as it has very high chances of failing. Who would take such a great risk to fund this trial? Isn't it more meaningful to fund trials for progressive disease such as siponimod or ocrelizumab? Or then remyelination trials?IMO, it would be easier to fund such trials and if they are successful they would be more beneficial for pwMS.

    1. MSRA receives over $2m funding a year. Dunno the UK numbers. Not saying MSRA should fund such a trial, but clearly there is a way to tap into the donors. From time to time, MSRA writes about very rich socialites who have donated lots of money to MSRA… if only someone would convince these very rich socialites that people with progressive MS are important and that there will be plenty of opportunities for benevolent photography sessions in return for their donations… heck, imagine if the UK MS society took this up as a cause and did some special fundraising for it…………….

  8. Unfortunately even at a "leading" specialist hospital (UK) I found the attitude was "so you have PPMS… too bad, there's no treatment" – and no further interest in me as a patient with this awful disease. Not even a mention of the possibility of exploring unlicensed or off label drugs. Is Barts the only hospital in the UK that will consider prescribing these?

  9. I thought the MS doctors at Barts had big doubts about Fampyra as a treatment for MS, thinking it might help in the short term (the kind of timescales used in this trial) but cause accelerated nerve damage in the medium term. Was I wrong about that?

  10. I've only just seen this post, this is a real shame. From my perspective – wheelchair user, spms and rapidly deteriorating manual dexterity – there is a real demand for this kind of research but I understand that if you can't get pharma interested, it's going nowhere.Many thanks to TeamG for caring about us and all their hard work on this project over the last year.I've also just noticed that the Oxford Dictionaries have made 'post-truth' their word of the year, worrying times!

    1. I don't totally agree. If pharma won't come to the table which they won't until some approvals occur e.g ocrelizumab or cladribine, then we have to try. We haven't waited. DrK has been performing off label treatment. A proper study has been planned for some time but the knockout back was get pilot data before the funders will have a look. Whilst Donald trump is building walls we are trying to build bridges to move this forward

    2. It may well do, they have not done the extra trials however the fact that they have said no so far must be a good sign.If EMA say no then there is no trial of oral cladribine in people in wheelchairs, it will have genric CLAD which is cost effective

    3. MD,I didn't mean to criticize TeamG in any way, I am a fan! It was just my Eeyorish delivery – not only is my glass always half empty but the bar is about to shut! I get told off for it all the time.I am aware of the off-label programme – I had an MRI and LP earlier this year with a view to taking clad. No active inflammation and my NFL count was on the low side of normal which is good news for me but won't provide any useful pilot data and would probably preclude me from any trial.And I was certainly not suggesting that TeamG are post-truthers, it is, as ProfG suggests in his post, those that ignore the results from previous trials.More bridges!!

    4. I didn't see it as a critisism. Of the people we have treated it is not all about neurofilament, but oligoclonal bands are also of interest. CLAD can kill B cells and plasma cells and is about the only MS drug that can get into and work in the CNS.

  11. I have SPMS and was given a wheelchair by the NHS. Needing to make extra income because I am unable to be in paid employment I trade shares on the stock market. That needs eyes and hands working OK. But getting to Moorfields eye hospital to keep my eyes working means using the wheelchair to get along station platforms and around the hospital but upper limb strength is lacking. I rely on the kindness of strangers for ramps, on Passenger Assist and taxi drivers. Station workers helpfully supply sticking plasters when I catch my fingers in the spokes. I am pleased the medical professional have recognised that upper limbs are as important as legs, more so when the legs are messed up by MS. (Deep core muscle wastage of the lower back, according to a physiotherapist.) If there is something that will help by arm and hand control and strength while leaving my brain useful bring it on, please? Who do I need to lobby for you?

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