Barts-MS rose-tinted-odometer ★★★★★
I am en route to a ‘Pathways to Cures’ meeting in Washington DC hosted by the National MS Society. The aim of the meeting is to refine the ‘Stop, Restore, and End Pathways’ for MS and to develop an international consensus on what an MS cure looks like. I am honoured to be invited to participate in this meeting and would like to thank the NMSS for inviting me.
As always I feel like an imposter; a neurologist who dares to dream about being a public health doctor hoping to someday be in a position to say we have prevented MS, at least in a proportion of people.
Only yesterday I read a very inspiring essay in the New England Journal of Medicine by Sonia Vallabhm who carries a rare genetic disease that at some stage of her life will strike her down and result in her dying of fatal brain disease at a relatively young age. Instead of accepting her fate her and her husband have retrained as scientists to study her disease so as to prevent its consequences.
So many of the messages in her essay resonate with what we are trying to do in MS I, therefore, took a writer’s liberty of paraphrasing her essay from an MS perspective. Apologies about the blatant plagiarism; I hope Sonia and the NEJM will forgive me!
If you have time please read her essay before reading my ‘fictional’ take on her messages. Sonia’s writing skills are clearly superior to mine, but the issues she raises are very clear. If you are at risk of a preventable disease that destroys the brain, why wouldn’t you want to know about being at risk of acquiring the disease in question and why wouldn’t you want to prevent the disease?
Sonia Vallabh. The Patient-Scientist’s Mandate. N Engl J Med 2020; 382:107-109.
Eight years ago, at the age of 24, I learned that I had a 1 in 4 chance of developing multiple sclerosis. In response, I left my fledgeling career in law to retrain in biomedicine. Starting in night classes and entry-level laboratory jobs, I earned a PhD in biomedical research in the spring of 2018. I now have an established research group focused on the prevention of MS.
There is a proud tradition of activated patients driving science. Fellow travellers of this path may be familiar with the kinds of questions I fielded from day one, in particular, whether it was appropriate for patients, or potential patients, to work on their own disease.
My goal is prevention: to preserve at-risk brains, including mine, in full health. MS is a silent disease advancing slowly: the average patient with MS is unemployed 10 years after diagnosis, in a wheelchair by 20 years and has their life expectancy clipped by about 8 years. To the best of my knowledge, there have been no prevention trials. Previous clinical trials targeting so-called prevention have focused on preventing the second clinical attack, i.e. the conversion from clinically-isolated syndrome (CIS) to clinically definite MS (second attack), have generally confirmed the known efficacy of licensed disease-modifying therapies. However, predictive or at-risk testing provides an opportunity, and arguably a mandate, to aim for a higher goal: preservation of brain function and ultimately the full quality of life. This is important as a lot of brain tissue and cognitive reserve is lost prior to the first clinical attack in MS. This is why I want to prevent developing MS.
Because at-risk people have no clinical symptoms testing drugs as a primary prevention strategy based on an MS risk score will require testing drugs in normal people. This realization has defined my priorities for the past 5 years leading me to focus on EBV the likely cause of MS; in particular, EBV vaccination and the treatment of infectious mononucleosis. These treatment targets require a biomarker that can reflect vaccine and drug activity without a definite MS phenotype. My research programme has highlighted many other issues, for example, the need for validated tools for quantifying MS risk in the general population; appropriate recruitment infrastructure (high-risk and population-based registers); defining the presymptomatic natural history of MS; and proactive engagement with funders, public health officials and regulatory agencies. As this list suggests, redefining the aims of drug and vaccine development to encompass MS prevention leads to many new research goals and widens the relevant stakeholders we need to engage with.
In the area of MS prevention, it will take more than a patient-scientist partnership to drive this shift. Perhaps there is something peculiarly clarifying about defining success by honestly answering the question “What would you want for your own brain?”.
My assessment of plausibly relevant approaches was guided by my bottom line: Which approach would face the smoothest path to a first-in-human trial in healthy people at high risk of developing MS?
Guided by practicality, in 2017 we hosted a task-force to develop an MS prevention strategy (see PDF below). The potential for EBV vaccination to prevent MS was endorsed by all participants. Three years on, the building blocks of this program are advancing towards a clinical trial. The progress is slow, very slow, but we will get there.
On the patient side, an emerging task is to rally people who are at risk of developing MS. Currently, very few of those at known risk of developing MS is seeking prevention strategies. Many are counselled against seeking this information because an unlucky result is not actionable at present. I understand this argument, but there’s more to actionability than meets the eye. To succeed in the clinic, we will need to rally supporters behind a counternarrative, one that honours the opportunity that at-risk individuals have to contribute to rewriting the collective future of people with MS. This reframing will not persuade everyone at risk, but it will resonate with some. And, especially when dealing with an uncommon disease, every person matters; every voice matters.
For me, the journey from patient to scientist continues to reaffirm that pursuing at-risk testing was the right choice for me and my family — a decision that continues to empower me in new ways as the years unfold.
I still occasionally encounter the concern that there is a conflict of interest inherent in researching your own potential disease. But far from seeing a conflict of interest, I see an exquisite alignment of interests as I work with mentors and allies toward a trial testing a vaccine and/or drug I hope to take myself, to prevent the disease that threatens my and my families future.
CoI: multiple
Thanks prof, I really enjoyed her article. Yours does it justice for those without access.
The problem is in activating us in this regard – who really has a 1/4 chance of developing ms? I have a family history but it was a great aunt, I’ve not knowingly had glandular fever – thus would deem myself to be at population level risk.
I do have a memory of you doing a prevention post a few years ago about ebv vaccines when I realised the other tranch of diseases it causes. I think was an angle that would get more societal buy in!
Re: “who really has a 1/4 chance of developing ms ….”
A female identical or monozygotic twin when her sister is already affected. However, with better risk profiling we may be able to predict who is at very high risk of getting MS in the future. Would you want to know?
Would I want to know – yes – if there was scope to alter the disease course. It is the same logic as wanting to take a dmt at CIS stage when you had relatively benign symptoms. If no preventative strategy then probably not.
Prof G,
“Eight years ago, at the age of 24, I learned that I had a 1 in 4 chance of developing multiple sclerosis.” I have seen numbers relating to the risk of getting MS if you have an identical twin with the disease and if you have a parent with the disease. Where does the 1 in 4 come from?
“I am en route to a ‘Pathways to Cures’ meeting in Washington DC hosted by the National MS Society. The aim of the meeting is to refine the ‘Stop, Restore, and End Pathways’ for MS and to develop an international consensus on what an MS cure looks like.” This sounds very similar to the NMSS Promise 2020 initiative which started fund raising in 2005. Promise 2020 raised the funds, but the projects never delivered ie in 2020 there are no available therapies to stop MS (stop progression), restore any function, or prevent MS.
I fully support your desire to prevent MS. Everyone I know with MS (including me) recalls a bad case of mono / glandular fever in their teens. One friend was diagnosed with MS some 9 months after having another case of mono / glandular fever in his mid 20s. The answer to preventing MS is staring researchers in the face and has been since the 1980s. Get an ebv vaccine and target children of those with the disease (use the MS websites to promote vaccination). Scientists / researchers spend too long focusing on protocols, sample sizes, measure tools etc. If you had a fire in your house you’d turn the outside tap on, plug in the hose, and put the fire out. If you stood there pondering about the water pressure to use, whether the hose should come through a window or doorway etc. you wouldn’t have a house left.
Good luck in Washington. “Get prevention done” (I’m plagiarising from Boris’s Brexit slogan).
Sorry – Promise 2020 should read Promise 2010
Sound like you have an identical twin to get a 25 percent risk.
Re: “Promise 2020 raised the funds, but the projects never delivered ie in 2020 there are no available therapies to stop MS (stop progression), restore any function, or prevent MS.”
Promise 2010 was about progressive MS; I think we have delivered a lot since 2005 when the initiative started. We now have two licensed treatments for progressive MS and a much deeper understanding of the biology underlying progressive MS.
Re: “Get prevention done”
I like it but is easier said than done. The anti-VAXX movement has made health policymakers and politicians nervous.
It would be easier, if researchers finally started doing widespread MS trials with various antivirals. That would be the strongest indicator (if successful) to push EBV vaccinations for MS prevention.
The only antiviral treatment I saw in the past couple of years was done in Australia (quite successfully).
Prof Pender I think
“Prof Pender I think”
Yes..and I think you pretty much trashed the study:
“Perhaps this is what we have been hoping for, but come on I say, look at the result. It is hardly the end of MS.”
https://multiple-sclerosis-research.org/2018/11/ebv-immunotherapy-works-in-ms/
Thanks Prof G. It’s a sad state of affairs where sick people have to retrain to treat, investigate and advance knowledge of their own disease. Simply because of the greed of pharma who are not interested in finding cures for any condition except treatments to keep the cash flowing. Until governments, academics take a stance against pharma more sicknpeolenwillnbe spending their precious time training to cure themselves. Pardon the punn. Its truly SICKINING. Those who shrug their shoulders and say what can I do and at the same time from the same gravey train. Are akin to those who nazi guards at concentration camps saying we just followed orders. You know who you are!!!!
The cure for hyperbole continues to elude us too, it appears.
Yes, maybe. So is stating sick people retraining in their twilight years to cure themselves. And if its hyperbole. Name one cure found in the last 10 years by pharma?
Solvadi found by Gilead as a cure for Hepatitis C.
You’re welcome.
What else have the Romans done for us?
Okay. Not all pharma are cut from the same cloth. I give you that.. Standing down. But you know what mean is generally accurate.
How much are they charging for this?
In UK it’s about 43 large (significantly cheaper in Spain and Switzerland) for the latest combi pill Harvoni 12 week course, sounds steep but it is cost-effective in the long run as it is curative and patients don’t progress to liver failure and so effective that revenues are declining rapidly.
‘The cure for hyperbole continues to elude us too, ”
Some can make Hyperbole into Reality…Most can not.
“People still flat-out don’t believe the FDA was cool with it,” Minikel says. Afterward, one of the 25 scientists in the audience pulled Lander aside and said, “That was one of the best presentations I’ve ever seen.” Schreiber agreed. He alluded to a pharmaceutical company he’d helped set up early in his career. “Twenty-four years into that company, there was nothing to show for it. Not one thing,” he says. “For two graduate students who are not trained in science to come in and do what they did? Absolute forces of nature, savants. They keep seeing things that other people don’t see.”
https://www.wired.com/story/sleep-no-more-crusade-genetic-killer/
“In November 2004, Prop. 71 passed with nearly 60 percent approval. It created the California Institute for Regenerative Medicine, or CIRM, an agency tasked with administering the $3 billion and making the campaign’s lofty visions a reality.”
Fourteen years later, the money voters approved is nearly gone, and supporters of CIRM and the research it funds are preparing to ask the public for another $5 billion in 2020″
“Not a single federally approved therapy has resulted from CIRM-funded science. The predicted financial windfall has not materialized. The bulk of CIRM grants have gone to basic research, training programs and building new laboratories, not to clinical trials testing the kinds of potential cures and therapies the billions of dollars were supposed to deliver”
https://projects.sfchronicle.com/2018/stem-cells/politics/
It seems to.me that often we are afraid to make hard choices.
If we could prevent MS today, would we?
AYou go why wouldn’t we do that, however
You could largely eliminate Huntington’s disease within a generation if there was a will, but we haven’t.
We spend time trying to develop science to avoid the simple solution.that is technically feasible.
We could eliminate many rare genetic diseases if we ban first cousin marriages.
At best you have an extra finger removed at birth at worse you have death or severely disabled children requiring lifelong care. This costs the UK billions of pounds, I did a petition that was turned down….my MP didn’t want to discuss is because they thought it was racist… Are we frightened of doing what’s right just because we are frightened of upsetting the…,.Royal Family.
If the royal family want to modernise stop first cousin marriages but they will say that has dumped them in the shit they are in 🙂
soo… you are a researcher? you know…. I’m a kinda researcher too.. love to research into research chemicals and the like
I think there would be a lot of support for this
1) I suspect that any successful prevention would not only prevent someone from getting it but also prevent existing ms from getting any worse (even if I’m wrong it’s still worth pursuing)
2) in my teen and young adult years after seeing the devastation ms did to my mom I would have happily tried to prevent it. I knew the risk was much lower than 1 in 4 but still felt at risk and all my siblings and I worried about getting this disease too (I was the only unlucky one)
That said I do think in order to fully activate prevention efforts doctors need to start being more honest with patients about how crappy ms still is and the prognosis even with dmds. No one will be activated to prevent if they think it’s not that bad
Hi Prof G.
I’m conflicted about the following line: “the average patient with MS is unemployed 10 years after diagnosis, in a wheelchair by 20 years and has their life expectancy clipped by about 8 years. ”
I thought the outcome is much better now with DMTs and I believe having read posts here with a much more positive outlook. Am I wrong? Or should I take these number as the true average sad reality?
Thank you
Oooops
🙂
?
“Oooops”
“?”
Looks like the Cherry Kool Aid Powder got diluted..and The Emperors New Clothes were not ironed.
” “the average patient with MS is unemployed 10 years after diagnosis, in a wheelchair by 20 years and has their life expectancy clipped by about 8 years. ”
I thought the outcome is much better now with DMTs and I believe having read posts here with a much more positive outlook. Am I wrong?”
Are you wrong ?..No..but uncomfortable
truths that might get your posts censored in the Siberian Spam Bin..or worse labeled a Killjoy..
Cynic..HSCT Zealot = Neo-CCSVI..or Troll.
Isn’t science wonderful..?
I think it may be time for the permanent naughty step anono.