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’ phases. 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."

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