2014 – the year of the 4P’s: prevention, prevention, prevention and prevention

2014 4P’s: prevention, prevention, prevention and prevention! #MSBlog #MSResearch

“I arrived back yesterday from a short break with my family for
the holiday season in South Africa. It was probably the first ‘real’ break I
have had from work in a decade; i.e. I didn’t respond to any emails or make any
posts on the blog. I managed to catch-up on lost sleep, read some great books,
argue and talk to my daughters, speak to my wife, eat good food and discover
some new wines, and reflect on the things in general. I feel refreshed.”

“2013 may or may not have been a momentous year for MS; it
depends on your world view or perspective. Alemtuzumab getting a 1st-line
licence in Europe is definitely my high-point from the 2013 MS calendar. In
contrast, alemtuzumab not getting a license from the FDA is my low point. The
contrasting decisions of the EMA and FDA needs some serious discussion, which
will no doubt take place over the coming weeks and months.”

“I am beginning to realise that the most important, and often
neglected, aspect of the scientific enterprise is the dissemination and
adoption of scientific innovations. This is why in 2014 we are going to spend a
lot of effort focusing on dissemination and improving the way we communicate. Education is the single most important driver
of change. We need to improve our skills as educators so that we can become
better communicators.”

“2014 is the year of the 4Ps; prevention, prevention,
prevention and prevention.  Focusing on
my ‘tube map’ of ‘An holistic approach to MS’ the 4Ps can be mapped to the
different phases of MS.”

Prevention 1 – the ‘at risk’ phase: how can we educate
people at risk of getting MS about strategies to prevent them from developing
MS. We plan to study our ‘Digesting Science’ programme formally to see if it
gets across the message of MS prevention to children of MSers. We will also
continue to expand the programme with the aim of disseminating it as widely as
possible. We are going to renew our efforts to get funding to study how EBV
causes MS. Is there a way we can intervene early, by targeting EBV, to stop the
immunological cascade that inevitably leads to MS in individuals who are
high-risk of developing MS? Will we be able to convince the grant reviewers
that this a worthy programme of research? If we don’t try we will never find out.

Prevention 2 – ‘diagnostic and minimal impairment’ phases.
We will continue to promote and study the impact of early effective therapies
on the course of MS and the paradigm of treat-2-target of NEDA (no evident
disease activity). We have the tools to do this already. What we need to do is convince
the regulatory authorities, payers and the field in general that this is the
only way we are going to prevent, or delay, MSers from becoming disabled in the
future. I personally believe we need to adopt a zero-tolerance (ZeTo) strategy
with regard to inflammation in MS. We are therefore in the process of designing
a pragmatic randomised controlled clinical trial of testing the ZeTo strategy. MSers
will be randomised to a current standard of care algorithm versus a ZeTo
management algorithm; the primary outcome has yet to be determined, but I would
support a surrogate of secondary progressive MS as the outcome. At the end of
the day we need to prevent end-organ damage and hopefully progressive MS. 2014
will also be the year that the INSPIRE trial is completed – our first clinical
study under ‘The Charcot Project’ banner. Imagine the impact if raltegravir, a
drug that targets HERVs and possibly herpes viruses, has a disease modifying
effect in MS? If we manage to complete our recruitment by the end of February
we should have results for you before the end of the year.

Prevention 3 – ‘minimal and moderate impairment’ phase. We
will continue to explore neuroprotection strategies to slow down, and hopefully
stop, progressive MS. The PROXIMUS and SMART neuroprotection studies will start
recruiting in 2014 and we should complete the Phenytoin in acute optic neuritis
trial in 2014. We will also be applying for funding to study the role of innate
immunity in driving progressive disease. Results of the laquinimod studies have
made us realise that this is an area that needs much more attention. The good
news is that Pharmaceutical Industry is also interested in targeting innate
immunity so we may see more add-on studies in the near future targeting innate
immune activation, in particular the microglial response.

Prevention 4 – ‘minimal, moderate and severe impairment’
We will continue to focus on strategies to prevent complications from the
symptomatic problems that MSers have to endure. One of our focuses will be on the
prevention of bladder, or urinary tract, infections (UTIs). The economic and
social impact of UTIs should not be under-estimated; it is massive. In
addition, there is emerging evidence that MSers with recurrent UTIs do worse in
the long-term. Another clinical focus of ours is the prevention of falls and
fractures. It is easy to assume that this issue is in hand, but it is not. I am
continuously arguing with family doctors to adopt a simple bone health programme
in MSers as one small way of trying to prevent fractures in MSers. The problem
with the latter is that it is based on data from old ladies with thin bones.
What we need is data from the field of MS. We are therefore collating audit
data that will hopefully support a national study to see if active intervention
programme can prevent falls and fractures in MSers and that the programme is
cost-effective.  Evidence-based medicine is
the mantra payers and regulators respond to. We will continue with our
commercial activities to develop a new class of anti-spastic drugs for MSers
with spasticity. We should be in a position to start a phase 2 clinical trial
in 2014.

2014 is looking like it is going to be a very busy year; what is highlighted above is only a small part of what we are actually doing across UCLP in relation to MS research.”

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • Thanks Prof G. Some hope for the new year. Are we likely to hear anything about remyelination in 2014?

    Ps i'm envious of your holiday. Would love to get a break from MS just for a day.

    • There are remyelination studies starting this year in MS. For example, bexarotene is a drug that is being tested in Cambridge. There is very little evidence supporting that MS is due to remyelination failure. If you stop the inflammation remyelination occurs spontaneously.

    • if you have early MS and are fortunate enough to have be treated with two cycles of Alemtuzumab you have a greater than 50% chance of taking a very long break from having MS; that is excluding the monthly blood and urine monitoring. It is unfortunate that American MSers won't have this option available to them.

    • MD can you be more specific on remyelination studies in the US this year? Also, Dr. G in a previous post the need for neuroprotective agents as well as immunomodulatory drugs are needed for successful spontaneous remyelination to occur. Are any neuroprotective drugs close to clinical trials?

    • This was announced at the Tykeson meeting in Denver but as the work is not yet published I feel it is not my place to give details of the drug or the trial design, which I have rudementary details but this study originates in California.

      There have already been a few some are ongoing as we speak and there aremany more planned for the nearer future

  • Prof G,

    Thanks. Glad you had a good break.

    From the response above, I'm guessing that you don't think remyelination treatments will have much effect. Why do you include remyelination treatments in your treatment pyramid? What about anti-lingo, are you not very hopeful that this will be successful? Many of us need some sort of repair treatment – even just a 1-2 point EDSS reduction. Do we havv any chance?

  • Re the above post, I think the best way we can have a small improvement in our EDSS score is to have our own plan based on holistic treatments and our own efforts.If I understand it correctly, I am on Tysabri which stops things getting worse. The body will remyelinate some of the damaged cells giving us the chance to use exercise to improve walking and balance. I had some improvement in 2013 and want another one this year!.

  • Thanks and glad you managed to grab, and enjoy, a proper break over the Christmas period. Would you please update us on the progress of the raltegravir trial, as the Charcot project info on the blog hasn't been updated for a while? Thanks v much, and like previous posters say, very pleased the whole team is 'rooting' for us 🙂

By Prof G



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