Boosting Immune Cells

Anne Kingston, reporter and senior writer at Maclean's Magazine, has just published a fantastic interview with pioneering neuroimmunologist Michal Schwartz.   I've recommended Dr. Schwartz's new book, Neuroimmunity: A New Science That Will Revolutionize How We Keep our Brains Healthy and Young, on this blog.  I'm thrilled that Anne not only read the book,  but got in touch with Dr. Schwartz and interviewed her, to learn even more.
http://www.macleans.ca/society/health/a-healthy-immune-system-is-the-key-to-a-healthy-mind/

I found this particular question especially insightful.

Anne Kingston: Your research indicates the immune system needs to be boosted, not suppressed. Doesn’t that run contrary to the immunosuppressant therapies routinely prescribed for many autoimmune diseases?

Dr. Schwartz: I’ve told everyone for a while to be careful when prescribing any anti-inflammatory drug for any neurodegenerative disease. They understand, but don’t have an alternative.

In other words, since there's nothing better, neurologists haven't changed their treatment target.  They understand that immune suppressing drugs (also known as anti-inflammatory) are keeping helpful immune cells away from the brain, but they don't have anything else they can prescribe which is FDA approved.  Here's more on the FDA pay to play system, which is maintaining the current $20 billion a year MS treatment industry.
http://ccsviinms.blogspot.com/2013/10/the-fda-and-multiple-sclerosis.html 

The last several years of research have directly questioned the current MS treatments.   Recent discoveries of the brain's lymphatic vessels and connection to the immune system and the neuroprotective role of immune cells.  The fact that the brain is not immune privileged and needs immune cells to repair the blood brain barrier.  The glaring fact that this immune cell and lymphatic cleansing system is relient on functioning venous drainage system  ---- in light of all of this research, the continued silence of the MS community is deafening.  They carry on as if nothing has changed, still prescribing immune cell sequestering and ablating medications, without a second thought.  They ignore vascular issues and the compounding evidence that cardiovascular lifestyle intervention can modify disease progression.   

Why?  They understand the science, but they don't have an FDA-approved alternative to sell MS patients.

Readers of this blog know that the current mouse model for MS, called experimental autoimmune encephalomyelitis (EAE) is not an appropriate model for MS.  EAE it is initiated by injecting the mice with lots of stuff we certainly don't find in the CNS of humans with MS, in order to create an inflammatory reaction.

Did you know that the MS drug Copaxone was originally created in an attempt to CAUSE the animal model of MS?   It was formulated to give mice EAE?  That's right.
http://www.ncbi.nlm.nih.gov/pubmed/20106343 

Glatiramer acetate (GA) was created in a lab over 40 years ago to cause EAE.   It consists of four synthetic protein compounds combined together to replicate myelin basic protein (MBP.)  Myelin basic protein is what the immune system damages in MS.  So, the idea was, inject the animals with this myelin-like formulation, and the immune system would go to town and attack ---creating an MS-like disease process, and disabling the mice.

What actually happened, however,  was the exact opposite. The animals injected with GA could not develop EAE.  What happened was that this formulation did indeed activate t-cells and boosted an immune reaction,  but these t-cells were not damaging, they were protective.
http://www.jimmunol.org/content/186/4/1887.full.pdf

This is how Copaxone was developed to treat humans--what MS researchers like to call serendipity, I think is essential to understand.  Copaxone is not an immune ablating or suppressing drug, it is an immune boosting drug.

Glatiramer acetate, now called Copaxone, was created in a lab at the Weizmann Institute in Israel. Not coincidently, this is the same institute where Dr. Schwartz has been conducting her research.  It would be the discovery of how GA increased the body's t cells and protected axons which would coincide and overlap with her studies.

Boosting immune cells, instead of suppressing them, protects the central nervous system. 

Granted, we now know Copaxone is most certainly not a cure for MS.  Although it blocked EAE in mice, its longterm efficacy in humans with MS is more of a mixed bag.  But what the creation of Copaxone should have instigated, at least in mind, were questions regarding the long-term safety of serious immune ablating treatments for MS and the development of immune boosting and modulating treatments.

"They understand, but they do not have an alternative."

Let's continue to put pressure on MS researchers for alternatives.  For immune modulating treatments, for venous treatments, for cardiovascular therapies, for immune boosting treatments. It's vitally important to study the endothelium, the connection between the vascular and immune systems.

Until we understand more, please be careful with serious immune cell sequestering MS drugs (like Tysabri, Gilenya, Tecfidera) or immune ablating chemotherapies (like Campath and Lemtrada.)   Do everthing you can do to live your best vascularly, endothelially, heart-healthy life.

The research keeps coming in.  And we do not know what we do not know.

be well,
Joan

The brain needs immune cells

In 2010, Dr. Alasdair Coles, an academic neurologist at Cambridge University, said to the press:

'We know MS is an auto-immune disease because if you block the immune response with drugs, people get better.'
This now infamous quote from Dr. Coles came when he was asked to comment on Jeff's treatment for CCSVI, as reported in the UK's Daily Mail.

http://www.dailymail.co.uk/health/article-1242441/Could-multiple-sclerosis-caused-blocked-veins.html

In my mind, linking the cause of MS to how the drugs work (for some) is akin to saying, 

"We know the earth is flat because we don't fall off!"
The relationship between the brain and immune system is much more complex than ever imagined.

Labeling MS a classic autoimmune disease is a serious misnomer--since we see the same immune cell reaction to myelin after hypoxic injury and stroke.

Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx

http://www.ncbi.nlm.nih.gov/pubmed/26527183
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162361/

There are no antigen specific antibodies in MS. There is no specific immune target in Multiple Sclerosis.  

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1168912/ 
http://www.ncbi.nlm.nih.gov/pubmed/26265268?dopt=Abstract

And, thanks to new research, we now know that immune cells are vital to a functioning brain.  

1.They provide healing after a break of the blood brain barrier, as we see in MS.
http://www.pnas.org/content/113/4/1074.abstract
2.They aid healing of axons after injury to the central nervous system, via glial scar formation
http://www.ncbi.nlm.nih.gov/pubmed/24756949
3.The "autoimmune" t cells often ablated in MS treatment are also responsible for neuroprotection.
http://www.ncbi.nlm.nih.gov/pubmed/12374425

At the time of his quote, Dr. Coles was bringing his life's work to market--the chemotherapy drug Alemtuzumab, repackaged for MS as Lemtrada.  Cole's overarching premise in his research is that the immune cells in multiple sclerosis are completely damaging to the brain, and need to be entirely removed.

And his theory then that "people get better" when the immune system is ablated is actually not true.  Yes, inflammation is tamped down in those with RRMS.  But, just like swatting a pesky fly with a sledgehammer, there is a lot of residual damage.   Immune ablation with chemotherapy has a host of horrific side effects, including fatal cancers, fatal viral and bacterial infections, worse autoimmune reactions in other parts of the body including kidney failure, lung tissue swelling, and hypothyroidism.  Not necessarily "all better!"  Which is why this medication has a black box warning, 

http://www.fda.gov/downloads/Drugs/DrugSafety/UCM426512.pdf

Meanwhile, Dr. Coles is busy trying to create an antidote to stop the new autoimmune diseases his drug has caused.  That's right...Lemtrada actually causes autoimmune disease!
The principal adverse effect of alemtuzumab (Lemtrada) is autoimmunity, which arises when reconstitution of the immune repertoire after alemtuzumab occurs by homeostatic expansion of residual lymphocytes. Therefore we are now testing the ability of keratinocyte growth factor to promote thymic lymphopoiesis and so prevent autoimmunity after alemtuzumab, in a MRC-funded clinical trial.
http://www.neuroscience.cam.ac.uk/directory/profile.php?Alcool

Even worse,  the MS disease process does not stop with Dr. Cole's Lemtrada.  Cerebral atrophy and disability continue, even without any new lesions.

Unfortunately, this did not lead to a clinical improvement in the disability in these patients. In fact, their disability worsened with time at a rate of 0.02 EDSS points for each patient each year. Evidence for continued neurodegeneration in these patients was shown by progressive cerebral atrophy on follow-up MRI scanning. 
http://europepmc.org/articles/PMC3629751


In the past decade, a narrative developed in the MS drug industry by MS researchers like Dr. Coles:  the idea that the immune system is at fault, and needs to be halted.   This has led to the creation of a class of drugs which create "lymphocyte sequestration" and "lymphocyte depletion"---meaning they keep the white blood cells walled off in the lymph tissue or deplete them, keeping them out of the body's circulation.  Instead of allowing immune cells protective entry into the body and around the brain, they are held back.  This new class of more powerful disease modifying drugs include Tysabri, Gilenya and Tecfidera.  

Not surprisingly, there is a price to pay when you hold back immune cells, deplete them, and don't let them do their job.  And one of those side effects is the reactivation of latent viruses and bacterial infections, including the John Cunningham virus (JCV).  This virus causes the deadly brain infection, progressive multifocal leukoencephalopathy (PML).  

Neurologists have comforted their patients regarding their PML risk and Tysabri use, telling them that if they were tested as JC virus negative, they would remain that way and not to worry.   But this was simply not true.  

The JC virus is very common in the general population, infecting almost 90% of us in childhood.  It stays under control and latent because our immune system keeps it in check.  This means we have a JC negative status.  The virus is able to cross the blood brain barrier where it attacks myelin and destroys brain tissue.  

New research shows that the risk of JCV reactivation due to Tysabri use is ten times higher than previously estimated.  That not 1%, but 10% of all patients on Tysabri were seen to go from JCV negative status to JCV positive status while taking Tysabri.  The drug is apparently what turns people from JC virus negative to positive.  This makes sense, if you understand that what Tysabri is doing is holding back immune cells, and rendering them unable to stop a virus from reactivating.

http://nn.neurology.org/content/3/1/e195.full

It also makes sense as to why Tecfidera and Gilenya have now been linked to PML...and I fear it's only a matter of time until real world reporting comes in showing JCV reactivation on these drugs.
                                                              +++++++++++++  

Dr. Michal Schwartz has been publishing on the importance of immune cells for brain health for decades.  Both she and Dr. Nedergaard are two of my research heros.  They are brilliant, determined women who have challenged the neurological status quo and are actively publishing their findings.

Dr. Schwartz explains her decades long search in understanding the importance of the immune system for the brain in her new book,  Neuroimmunity: A New Science That Will Revolutionize How We Keep Our Bodies Healthy and Young.
http://www.weizmann-usa.org/media/2015/09/22/prof.-michal-schwartz-will-change-your-mind

This book is simply wonderful!  It is written clearly and simply, so that lay people might understand her research.  But it is also in-depth enough to appeal to researchers.  All of her publications are cited.

Scientists long believed that there was no communication between the brain and the immune system; in fact, it was thought that any infiltration of immune cells into the brain was a major threat to our health. Based on this assumption, the standard treatment for inflammation associated with neurodegenerative diseases, such as Alzheimer’s, was to totally suppress the body’s immune system.

Prof. Schwartz turned this theory on its head by proving that the immune system and the brain do “speak” to each other – and that, in fact, neurodegenerative diseases are the result of a communication breakdown between the brain and the immune system. Instead of suppressing the immune system, she argues that the most effective way to treat Alzheimer’s and other chronic neurodegenerative diseases is to do the opposite: boosting targeted immune cells in the brain. 

The brain needs immune cells.

Please, if you have MS--- until we understand more about the immune system and brain health, make sure to discuss this new research with your neurologist, especially if they are putting pressure on you to try these new immune ablating and lymphocyte depleting drugs for MS.  New research is coming in every single day, showing that this method might not be the best approach for long-term brain health.

Be well, be curious.
The earth is not flat.
Joan

Still skiing, Dr. Miller

This month is the 8 year anniversary of Jeff's diagnosis with Multiple Sclerosis.  (Although we now believe Jeff has had MS since childhood, when he lost his peripheral vision.  Throughout his life, he would exhibit other common MS symptoms, but he wasn't officially diagnosed until age 43.)

We are happy to share that he remains MS progression free, is still jogging, working full days, traveling the world, composing, performing and conducting,
and yes, Dr. Miller, Jeff is still skiing.

Neurologist Aaron Miller confronted me at the CCSVI Alliance table at the American Academy of Neurology Brain Fair in 2013.  He walked up to our exhibitor's table, looked me in the eye and laughed in my face.  "You can't possibly believe this!"  he sputtered.

I told him that for many, there was a vascular connection to MS.  That my husband had regained his balance and energy and was able to return to walking, then biking, then jogging and eventually skiing.  All thanks to his successful venoplasty treatment which repaired his stenotic dural sinus and jugular veins and his implementation of the endothelial health program.  Dr. Miller guffawed,  "That's ridiculous!   There's nothing to the vascular business.  Veins?  We've discredited it all.  Well, let's hope he keeps skiing! Ha!!"

He smirked at me as he walked back into the conference, where he was presenting on the latest oral drugs for MS.

"The future has never looked brighter for [people with] MS," says Aaron Miller, M.D., medical director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center in New York City. And, he adds, "I anticipate that in the [near future], we'll have perhaps another four new multiple sclerosis drug treatments."
http://www.healthcommunities.com/multiple-sclerosis/treatment.shtml

Dr. Miller would end up backing away from one of the new oral medicines, Gilenya--after there were six deaths linked to the drug.

The deaths have “made me a little more cautious,” Aaron Miller, chief medical officer of the U.S. National Multiple Sclerosis Society and a medical director at New York’s Mount Sinai Hospital, told Bloomberg News. “I am not somebody who has recommended Gilenya as a first-line drug prior to these reports, and I’m still not recommending it as a first-line drug until we get more data,” Dr. Miller added. Miller treats about 800 patients and has prescribed Gilenya to about 30.
http://www.newsinferno.com/doctors-back-off-gilenya-amid-safety-woes/

Dr. Miller was ready to embrace these new oral MS medicines, which he admits were lacking data, and promote them at conferences and prescribe them to his patients. Yet he deemed my husband's pursuit of vascular health and repair of a venous malformation "ridiculous."

Are MS specialists really concerned about their patients' health?  If so, they might want to consider the following:

Matt Embry is now 20 years past his MS diagnosis, with no progression.  He still runs marathons and works full time.  He's offering his program, called MS Hope, for free.  He has a website and Facebook page, where the program his father, Dr. Ashton Embry, compiled for him using peer-reviewed MS research, is now offering continued hope and health to those with MS.
http://www.mshope.com

Matt, Dr. Terry Wahls, Dr. George Jelinek and many others are speaking out about how nutrition, lifestyle, exercise, UV rays, vitamin D and smoking cessation can help people with MS maintain health and mobility.  And they are publishing their results in medical journals.
http://terrywahls.com
http://www.overcomingmultiplesclerosis.org

The International Society for Neurovascular Diseases will meet in March to discuss the ongoing studies on cerebral perfusion and CCSVI.
http://www.isnvd.org/d/Napoli

The keynote speaker for the ISNVD conference is Dr. Mat Daemen, Professor at the Academic Medical Center in Amsterdam and Project Leader at the Cardiovascular Research Institute in the Netherlands.  His recent publication,  “The Heart and the brain: an intimate and underestimated relation” discusses the important relationship between blood flow and the brain, and the lack of understanding of this connection, due to the non-collaborative and myopic approach of medical research.

The apparent lack of appreciation of the link between cardiac and brain (dys)function is probably due to monodisciplinary approach by cardiologists and neurologists and by the reductionist approach of modern medical research.  
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547419/

Despite the MS treatment machine and pharmaceutical companies' best efforts, the vascular and environmental research continues.  Patients are finding healing and sharing with others.  People are donating money to directly fund the research which interests them and are participating in this grass roots movement.    There are things that people with MS can do for themselves today, which will make a difference in their disease progression tomorrow.

If I was an MS doctor and someone told me that their 50 year old husband with MS had returned to skiing after having trouble walking and balancing, I might sit down with them and learn more.
Not laugh in their face and deride them, wishing them ill.

If I was an MS Society and a young man from my country began sharing his program for health and healing after having had MS for 20 years, I might ask him to speak to people with MS and help them.  Not consider his information a threat.

If I was an MS researcher, and a world-reknowned vascular specialist (who was collaborating with NASA) could show me how venous reflux was impacting the brains of people with MS, I might work with him.  Not spend millions on studies ignoring his protocol, just to prove this condition didn't exist.

But I am none of those things.
I've got no money in this game.  Just skin, and skis.

Joan