What is the most exciting MS research on the horizon?

I was asked about which paper I have written or co-written that has or will have the most impact in the field of MS. There is little doubt that it is our report of our 2017 workshop on “EBV Infection and MS Prevention”.

This report (see below) was the catalyst for creating the Preventive Neurology Unit (PNU), which is embedded in the Wolfson Institute of Preventive Medicine. The funding for the PNU allowed us to employ Dr Ruth Dobson to be the academic lead on the MS Prevention workstream in the PNU. All we need now is a sterilising vaccine against EBV, the necessary funding so that we can set-up an international anti-EBV MS Prevention study and support from the public to do this study. Once we have all these in place we will be a position to finally test the hypothesis that EBV is the cause of MS. There is nothing in the field of MS research that excites me more than testing this hypothesis. Do agree? What excites you? Any other recommendations?

Smouldering away

As you are aware we, or I depending on your perspective, have recently have hit a brick wall trying to convince the MS community that the big unmet need in MS is smouldering disease.

The central hypothesis is that smouldering MS is the real MS. The following YouTube presentation summarises some of the main arguments for the hypothesis.

Your comments will help me make a decision to giving-up working on established MS and to focus on preventive neurology; in particular, preventing MS.

CoI: multiple

Building a Rocket

As I write this I am on the way back from an ‘atypical’ summer holiday with my family. We spent a week in the ‘Oude Land’, South Africa, celebrating my mother in law’s 80th Birthday and then a week in the subtropics for some warm sunshine. The internet access was dismal, which was a good thing that allowed me to switch-off, sleep, eat, exercise, think, relax and recharge my batteries. 

The insights learned, or relearned, is that my family are my priority and for quality reading and thinking time you need to take yourself offline for long as possible. One consequence of the latter is that I now have two inboxes with over 3,000 unread emails (panic). 

As I lay next to the pool I had ample time to contemplate life, the universe and all things MS. I came to the conclusion that the biggest threat to our field, at least in the short term, is dogma and groupthink. We are so entrenched in the MS autoimmune hypothesis that it is becoming increasingly difficult to see the light, and blue sky, because of the sheer depth of the autoimmune trench we have dug ourselves into. 

In Range: How Generalists Triumph in a Specialized World, by David Epstein, one of my holiday reads, I learnt that Arturo Casadevall believes that specialisation has created a ‘system of parallel trenches‘; everyone is digging deeper into their own trench and rarely standing up to look in the next trench over, even if the solution to their problem happens to reside therein. 

Using the trench analogy we are going to have to build a human scaffold several generations deep to get out of the trench the MS community has dug, or we could build a rocket. I can’t resist the rocket analogy. Whilst away I also read Loonshots: How to Nurture the Crazy Ideas That Win Wars, Cure Diseases, and Transform Industries by Safi Bahcall, which describes how out-of-the-box thinking has the ability to transform a field. 

Image from the Innovation Matrix

It is clear that the autoimmunity model has many flaws or as Safi Bahcall would say warts. As a result, it is becoming increasingly difficult to support the autoimmune hypothesis intellectually. Some of the holes in the autoimmune hypothesis have been rehearsed many times before on this blog. 

  1. Dear MSologist, why am I progressing despite being NEDA?
  2. What is causing my accelerated brain volume loss when my disease is in remission?
  3. You say I am in long term remission, and possibly cured, from MS, but my last CSF analysis shows that I am still oligoclonal band positive? Why?
  4. My head is full of slowly expanding blackholes. Can you please stop them expanding?
  5. There is an epidemic (increasing incidence) of MS in Scotland and almost every geographical area studied. Why? Is the increasing incidence explicable by the autoimmune hypothesis?
  6. If MS is an autoimmune disease please tell me why your immunotherapies are only partially effective at preventing disease activity and worsening disability?
  7. How do you explain the early Prineas MS lesion; massive oligodendrocyte apoptosis without T- and B-cell infiltration?
  8. Why does rebound happen post natalizumab and fingolimod? And why are anti-CD20 therapies so effective in preventing rebound? How do these observations fit into the autoimmune hypothesis?
  9. What about the evidence that EBV plays such a pivotal role in MS? How does this fit in with MS being an autoimmune disease?
  10. Is the human endogenous retroviral or HERV activation within the peripheral and CNS compartments of MSers simply a bystander phenomenon or part of the disease? Are HERVs a non-specific trigger of autoimmune disease? 
  11. Does the memory B-cell data and hypothesis sit comfortably with MS being an autoimmune disease? Could this be explained by EBV alone? 
  12. Does the strong MHC association with MS have to be due to autoimmunity? Could the MHC link be explained by an infection or dual-infection hypothesis?
  13. How does the epidemiological data on vitamin D, childhood/adolescent obesity, smoking, solvent exposure, HIV and MS, explain autoimmunity? 

It seems to me that most people in the field of MS are content with fitting a square peg into a round hole. I am not. So what am I going to do about all my angst and increasing doubts? We have been trying to do something about it with our Charcot Project and our Preventive Neurology Unit, but things are happening too slowly. What we need is a turbocharge – a rocket –  to accelerate our programme of work. In short, we need people, resources and money. Therefore, the 2019/2020 academic year will be a year of grant writing focusing on MS prevention and loonshots.