Over the counter antihistamine may stimulate myelin repair

[MStranslate]

A small, Phase II clinical trial has shown that a common over the counter antihistamine, called clemastine fumarate, has the ability to partially reverse damage to the optic nerve in people with multiple sclerosis (MS). This release comes ahead of the researchers from the University of California, San Francisco presenting their data at the annual American Academy of Neurology meeting being held in Vancouver, Canada between April 15-21.

This study arose from earlier work by Dr Jonah Chan, who invented a novel system to rapidly screen thousands of current medications for their ability to promote myelin repair. Using this system, clemastine fumarate (an oral allergy medication) was found to stimulate myelin regrowth. To assess the impact in people with MS, this Phase II trial recruited 50 people with MS (average age = 40, average time since diagnosis = 5 years) that all suffered from chronic optic neuropathy, resulting from myelin damage to the optic nerve and causing loss of vision.

As part of the 5 month study, people received either clemastine fumarate or a placebo for the first 3 months, followed by the groups being switched for the remaining 2 months. Vision tests were performed at the beginning and end of the study. One of these tests, called a visual evoked potential test, measures the time taken for a signal to travel from the retina to the visual cortex. As the speed of nerve signal transmission is altered by the myelin sheath, this test can be used as a marker for myelin repair. Based on these results, a moderate improvement was seen in the transmission time in people that were taking the antihistamine. A reduction in vision impairment was also observed, however, this was not statistically significant. People taking the antihistamine treatment also reported a modest increase in fatigue levels. This finding suggests the potential for clemastine fumarate to reverse damage and promote myelin repair in the optic nerve of people with MS.

Dr Ari Green, the lead researcher on the project, believes that “this study is exciting because it is the first to demonstrate possible repair of that protective coating in people with chronic demyelination from MS”. Whilst he admits that the “improvement in vision appears modest”, he reinforces the importance of the study and suggests that it will hopefully provide “a framework for future MS repair studies and will hopefully herald discoveries that will enhance the brain’s innate capacity for repair”. They are also currently working on more powerful treatments with less side-effects.

Dr Green emphasises the need for larger studies to confirm these results before doctors could recommend this treatment to people with MS. It is known that clemastine can have potential side-effects and it should also be noted that the dose used for this study is above that recommended for over the counter use.

[cheerleader]

Myelin repair??? This is nothing but market hype and supposition.
Here's the PR release from Vancouver, BC
http://www.prnewswire.com/news-releases ... 50376.html

During the study, delays were reduced by an average of slightly less than two milliseconds in each eye per patient among those who received the antihistamine.

Remyelination is simply a supposition on the method of action. Evoked potential is one way to suggest improvement, but it does not define the process. And this improvement is negligible. They didn't show remyelination on MRI in these participants.

One of the biggest difficulties in the development of remyelination therapies for MS is the demonstration of remyelination in living patients. Indirect measures, such as improvements in neurophysiological outcomes, such as electroencephalography, evoked potentials, optical coherence tomography, and transcranial magnetic stimulation may suggest, yet not confirm, remyelination (144–148). Functional improvements could indicate remyelination, but could also indicate neuronal plasticity or the spreading of sodium channels into demyelinated internodes, which could also restore conduction in unmyelinated axons (144, 149, 150)

http://journal.frontiersin.org/article/ ... 00257/full

What the anti-histamine might actually be doing is reducing endothelial permeability, by blocking the histamine receptor. The method of action might be on the vascular endothelium….but still, it’s not much.
http://www.pnas.org/content/107/44/18967.full

And the side effect of FATIGUE? For people with MS? Jeff laughs at this….no way. Not worth it. He won’t take an antihistimine if he has an allergic reaction (cat or pollen), for same reason.
The claim of remyelination and “reversal of MS” is pure conjecture and market hype BS.

EGCG (green tea) has as good or better results in VEP, less side effects, but harder to make $$$
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585739/

You know what proves myelin repair? Actual remyelination of lesions on MRI, reversal of brain atrophy and lack of MS progression.
http://ccsviinms.blogspot.com/2015/09/celebration.html

cheer

[MStranslate]

Thanks for your comments cheerleader! Let me try and continue the conversation...

Myelin repair??? This is nothing but market hype and supposition.
Here's the PR release from Vancouver, BC
http://www.prnewswire.com/news-releases ... 50376.html

During the study, delays were reduced by an average of slightly less than two milliseconds in each eye per patient among those who received the antihistamine.

Remyelination is simply a supposition on the method of action. Evoked potential is one way to suggest improvement, but it does not define the process. And this improvement is negligible. They didn't show remyelination on MRI in these participants.

I think this is a really valid point cheerleader and one of the reasons why when I wrote the article about it, I said that it may reverse and that it is suggestive. I completely agree that to prove this they will need to include MRI data or another way of showing categorically that remyelination has taken place. As this was a press release about their upcoming presentation, I can't be completely sure that they haven't got this data and will present it at the AAN meeting. I am hoping to talk to Dr Green about the research and I will ask this very question if I get the opportunity, but unfortunately, no guarantees. I think the other point to make that somewhat supports an argument of remyelination is that their initial screening of all of these compounds (that led them to test clemastine fumarate) was based on looking into current drugs that have properties that allow for remyelination. Whilst this isn't conclusive and still requires the actual check that you described, it does give a bit more support to the argument that this is the reason for the change that they observed. Similarly, the response and change that they see is very modest - although statistically significant - and Dr Green mentions working on ones that have a stronger effect and less side-effects...

And the side effect of FATIGUE? For people with MS? Jeff laughs at this….no way. Not worth it. He won’t take an antihistimine if he has an allergic reaction (cat or pollen), for same reason.
The claim of remyelination and “reversal of MS” is pure conjecture and market hype BS.

EGCG (green tea) has as good or better results in VEP, less side effects, but harder to make $$$
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585739/

And this is also true - obviously something that increases fatigue isn't going to be amazing for people that already suffer severely from fatigue. If, however, this could lead to something that produces a very significant improvement in vision, then it would be a balancing act for people in terms of what was more important to them. The EGCG story is really interesting and one that I will be interested to see the clinical trial results. I don't think that the UCSF study is about making lots of money, that really isn't the goal of any researchers working on MS. I'll keep you updated if we find out more about this study based on their presentation.

[cheerleader]

Hi Brett--
Good to meet you. Happy to continue the conversation. I'm Joan (originator of CCSVI in MS on Facebook https://www.facebook.com/CCSVI-in-Multi ... 796282297/ and blogger on MS and the Vascular Connection http://ccsviinms.blogspot.com

I've covered current MS research on my blog since 2009. I brought Dr. Zamboni's research to Stanford in 2008, where my husband was the first treated for CCSVI in North America. It is now 7 years since his treatment, and his cervical lesions show remyelination and his gray matter atrophy has reversed, as documented on MRI. He is still quite active, with no MS progression since his diagnosis nine years ago. http://www.jeffbeal.com

During this time, we've all seen many compounds trialed as MS treatments. Universities have received funding and are looking at inexpensive blood pressure meds (like lisinopril) Vitamin B9/high dose biotin, antihistamines and other common inexpensive, generic drugs which they hope to repurpose, license, market and mark-up for MS. The new target is called "neuroprotection." And yes, it's about profit--not etiology.

Here's a paper on the neuroprotective qualities of ECGC http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775893/

I'm actually more interested in Dr. Jonathan Kipnis' upcoming presentation at the International Society for Neurovascular Disease at the Academy of Sciences on the newly discovered lymphatic drainage system for the brain, which relies on vessels draining through the venous system. His research will look at how these vessels function and how boosting and modulating immune cells may hold real answers for diseases of neurodegeneration. His lab is re-writing the textbooks. And getting us closer to disease etiology, not just another "treatment."
https://news.virginia.edu/illimitable/d ... table_3-16
best,
cheer/Joan

[MStranslate]

Hi Joan,

It's a pleasure to meet you - I don't know if you have had a chance to take a look at MStranslate to find out more about me...I'm an MS researcher based in Melbourne, Australia. During my time in research, it became very aware to me that a big gap existed between the people doing the research and the people that were actually impacted by this research. To bridge this gap, I co-founded MStranslate with my brother (background in web and social media), where we post up-to-date, independent, accurate, easily accessible and easy to understand summaries of MS research.

I'm actually more interested in Dr. Jonathan Kipnis' upcoming presentation at the International Society for Neurovascular Disease at the Academy of Sciences on the newly discovered lymphatic drainage system for the brain, which relies on vessels draining through the venous system. His research will look at how these vessels function and how boosting and modulating immune cells may hold real answers for diseases of neurodegeneration. His lab is re-writing the textbooks. And getting us closer to disease etiology, not just another "treatment."
https://news.virginia.edu/illimitable/d ... table_3-16
best,
cheer/Joan

It's funny you should mention this! I'm very much looking forward to it as well and was actually hoping to be able to attend - however, unfortunately as MStranslate is completely unfunded, the cost of travelling and attending both this conference and the AAN meeting were too much for us this year. However, when Dr Kipnis' research was first published, I managed to arrange an interview with him to discuss his work. You can view our conversation here:



Hope you find it interesting!

Cheers,

Brett

[cheerleader]

Hi Brett--
Yes, I have seen your video! And I've been to your site. Well done! Was very thankful you and your brother posted that terrific interview. Jony is brilliant, and a great guy---I'd been following his publications since his days at the Weizmann Institute with Michal Schwartz. It was thanks to their publications on the neuroprotective nature of the immune cells in the CNS, that we never considered immune ablating or lymphocyte sequestering meds for Jeff. We dodged that bullet, thanks to that work!
http://ccsviinms.blogspot.com/2015/06/d ... right.html

It's really a shame you can't be at the ISNVD conference...the researchers there are looking beyond the EAE autoimmune theory, and exploring the connection between the endothelium, vasculature and newly defined lymphatic system. Sharon Richardson and I (for CCSVI Alliance) reached out to Dr. Kipnis and put him in touch with the ISNVD, when we realized how his work fit in with the exploration of venous drainage. http://ccsviinms.blogspot.com/2015/06/a ... overy.html

Perhaps you can have Kerri Cassidy of CCSVI Australia report back for your site? I'm sure she'd do a great job. Kerri has real skin in the research game. As do those here on This is MS (which was started by people w/MS explaining the research for each other), and the 23,000 members on my Facebook page. As I'm sure you know, she's also brilliant and articulate (yet modest!) She will be at the conference with Dr. Kavnoudias for the presentation---“Randomised, Double-Blinded, Controlled (with sham) Study of Percutaneous Transluminal Angioplasty for Extracranial Vein Stenoses in Patients with Multiple Sclerosis.”- Helen Kavnoudias, PhD, Head of the Radiology Research Unit, the Alfred Hospital, Melbourne, Australia

Researchers I'd suggest you consider for video interview, who are outside the AAN viewpoint, yet have made impactful discoveries for MS and the brain:
Dr. Maiken Nedergaard and the U of R--her lab discovered the brain's lymphatic cleansing system which happens when we sleep: She has also recently published on the protective role of t cells in maintaining the blood brain barrier (!) I visited her lab in April 2015. She is brilliant. http://ccsviinms.blogspot.com/2015/04/g ... gaard.html

Dr. Michal Schwarz, the Weizmann Institute (mentioned above) who has gone up against the theory of an immune privileged brain for decades. She has written a great, lay person friendly book, published last fall. http://ccsviinms.blogspot.com/2016/03/b ... cells.html

And your country mate, Dr. George Jelinek. He has published many interesting papers on how environmental factors impact MS disease progression. UV rays, Vitamin D, nutrition, exercise, meditation--are all things people with MS can be doing for themselves, today, to maintain brain volume and keep disability at bay.

Hope you find these links helpful, Brett.
I think the gap between people with MS and their understanding of research is not that large. Everyone I have ever met with MS has a pretty clear understanding of their disease and current research. Having skin in the game creates the need to understand!

The much larger gap is between independent and meaningful research on disease etiology, and the $20 billion a year MS drug industry.
That's the cavernous divide I hope to bridge-- would love your assistance!

When you meet Dr. Ari Green at AAN, could you please ask him if he believes this might be a conflict of interest in the particular slant of his MS research?

Dr. Green has received personal compensation for activities with Inception Sciences, Mylan Pharma, Medimmune, and Bionure. Dr. Green holds stock and/or stock options in Inception Sciences. Dr. Green has received research support from Inception Sciences, Biogen and Novartis.

https://tools.aan.com/annualmeeting/sea ... 6&type=all

all best,
Joan

[NZer1]

Thanks Joan and Brett! ;)

[MStranslate]

Hi Joan,

Have just commented on the CCSVI in MS Facebook page in relation to this as well, but to keep the chat consistent across both platforms, I just wanted to clear up a slight misconception that I may not have been completely clear about. Due to lack of funding, we won't be attending either of the upcoming conferences in the US. I am currently working through the process of being able to still gain access to some of the researchers presenting at each and am hopeful that we will be able to do so - although it is much harder working from a distance rather than actually being present.

As for Kerri - she has been a huge supporter of MStranslate from the beginning and I have met her on a number of occasions. I was actually discussing yesterday the possibility of getting her to cover some of the New York conference for us and will be getting in touch with her shortly regarding this. We have shared some of her updates from international meetings previously.

Thanks for helping to raise awareness of what we do and I'll keep you updated on any progress we make in conference coverage. Thanks for the suggestions - I will add them to the list!

[cheerleader]

Thanks so much, Brett!
Apologies for misunderstanding. Forgive me! I thought that when you said you were going to talk to Dr. Green about the antihistamine presentation, that you were attending AAN. But I'd still love to know whether he believes his financial disclosure as a stock holder in the remyelination research he is presenting might be considered a serious conflict of interest.

I've edited and clarified my note on Facebook. Appreciate you checking in on here and there---and am THRILLED Kerri will be helping you make the ISNVD presentations accessible.
Thanks so much for all you're doing, Joan