Recent news about bexarotene inspires mixed feelings.

nerve cell

With MS research breakthroughs, it can often feel like “one step forward, two steps back”.  We read about some new study with incredible results, but then get to the bottom of the page and see the dreaded “further larger-scale studies are now required”.  Just like that we realise that this new treatment is probably 5 years away, if it ever makes it at all.  There are no shortcuts in science, as we are all seeing all too clearly in the frantic search for a COVID-19 vaccine.

Whilst these “hurdles” and processes can be very frustrating for those of us with MS, it is of course only right and proper that any new therapy is appropriately tested before it reaches the patient, ensuring that it is primarily safe, but also actually effective.

Bexarotene

One recent example is the skin cancer drug, bexarotene. The MS Society in the U.K. has just published some very important results from a phase 2 trial involving 50 people with relapsing remitting MS, all already taking a disease modifying treatment.  25 subjects were given bexarotene once daily for 6 months, whilst the other 25 were given a placebo.

Follow-up tests demonstrated that those pwMS taking bexarotene had evidence of increased nerve transmission rates in the visual pathways in the brain, and areas of new myelin production on MRI.  In short, remyelination had occurred in areas previously damaged by MS, and the speed of nerve signals had increased in an area of the brain commonly affected by MS. 

“Amazing news, where do I get it?!”, I hear you shout.

Well, unfortunately there is some bad news. Bexarotene is not going to be taken forward into phase 3 trials, as it was felt that the potentially serious side effects of under-active thyroid and increased levels of fats in the blood made it unsuitable as an MS treatment. This is very valid, it is already known that an unhealthy balance of fats in the blood can hasten disability progression, so it would be terrible if short-term gain with bexarotene were to be outdone by long-term loss.   

But this is not a reason to be down-hearted, far from it in fact.  This was a very well conducted study categorically demonstrating that remyelination is possible in people with MS.  Previous early studies had shown promising and similar results, but were primarily on mice. To prove the concept in humans is therefore a very important step forward, and was the primary purpose of this trial.  It gives researchers valuable insights into how myelin repair occurs, and where to target their future efforts.  If we could repair areas of damaged myelin, this could improve MS symptoms and potentially slow or stop disability progression.  Of course this is something that those of us living with MS are desperate for, but it must be done in a way that is safe. 

A perfect illustration is seen in another trial that is about to start in the U.K., this time using a combination of two drugs, both already widely prescribed and with excellent safety profiles. Metformin, an oral treatment for type II diabetes, and clemastine, an anti-histamine tablet used to treat hayfever and allergies, have both previously been shown to potentially promote remyelination.  But both studies were small, and in mice (in the case of Metformin) or not based on real-world clinical outcomes (with clemastine).  Combining the two and giving them to people with MS is therefore very exciting news.

So please take this for the good news story that it truly is.  More pieces of the remyelination puzzle have fallen into place, and we really are getting closer to the “holy grail” of MS research  all the time.


References:

1) https://www.mssociety.org.uk/research/latest-research/latest-research-news-and-blogs/trial-shows-myelin-repair-in-humans-is-possible

2)  https://overcomingms.org/latest/metformin-it-one-new-ms-wonder-drugs

3)  https://multiplesclerosisnewstoday.com/news-posts/2020/10/01/fast-forward-grant-remyelinating-compounds-ms/?utm_source=Multiple+Sclerosis&utm_campaign=bba77d4f87-RSS_NON-US_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_b5fb7a3dae-bba77d4f87-73576925

4)  https://overcomingms.org/latest/first-drug-shown-promote-remyelination

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Hide commentsShow comments

Dolores (not verified)

What a waste of time and energy to read this article, giving people hope and than at the end leaving them with nothing, bloody hell

Helen Tyzack (not verified)

The title of the article was clear - the wait goes on.

rico (not verified)

clickbait title, these things are known 10years about clemastine Metformin

Helen Tyzack (not verified)

Not every sufferer has access to all information so it is useful and beneficial to be kept abreast of research findings by OMS

STACKPP

With reference to the recent AI (Artificial Intelligence) Breakthrough on Protein Folding done by DeepMind, does anyone one here or within the OMS team know if this will have an impact on MS MS treatment or research? Thank You. Pete.

Lucy-OMS

Hi Pete,

Many thanks for getting in touch, it is a really interesting question. The short answer is almost certainly will have an impact on MS research, but at this stage it is probably not quite clear just how much.

The fact that A.I. can now very accurately predict the 3D structure of proteins based on its amino acid sequence is a gigantic step forward. At the very least, it is likely to significantly reduce the time spent in the early stages of the research process, not just in terms of new drugs, but also investigating the underlying biology of a particular disease. This in turn will hopefully speed up drug development and meaningful new treatments for patients.

This can only be a huge positive to the research community, and for those of us with MS.

At present I understand that it is focusing on new drugs for malaria and sleeping sickness, but as to how far it could take us, the sky really is the limit.

For example, in the current hot topic of COVID, it is protein structure that determines the antibody response to the virus, so I wouldn’t be at all surprised if it looked into that in the very near future.

It is a bit of a shame that one of the most stunning scientific advances of the last 50 years has been lost in the 24-hour news cycle to stories like COVID and Brexit, but nonetheless, it should be great cause for hope and optimism.

I have attached an interesting article on the topic that recently appeared in “Nature”, in case you would like to read a bit more.

I hope this helps.

Take care,

Jonathan

Reference:

https://www.nature.com/articles/d41586-020-03348-4