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

Dr. Michal Schwartz was right.

The last hundred years or so, all of neurological disease research has maintained that any immune cells which showed up in the brain were there for one of three reasons:  to protect the brain against infection, in an autoimmune reaction (as in MS) or during an inflammatory attack (as occurs after stroke or ischemia.)  But immune cells as part of a healthy, functioning brain?  Absolutely not!

MS researchers have continued this dogmatic narrative, based on the "successful" development of EAE and immune ablating and suppressing drugs.  They maintain that the brain is immune privileged, and the blood brain barrier is meant to keep immune cells out.  And they've been suppressing the heck out of MS patients' immune cells ever since.

Recent research from the University of Virginia and the Kipnis Lab has called all of this into question.  It now appears that a healthy immune system is connected to the brain,  Exactly as it is in all other organs, via lymphatic vessels which drain into veins.

But even before the U of V publication, there has been one researcher who has single-handedly challenged the dogma on the immune privileged brain.  She has asserted the need for immune cells in our central nervous system.   She has been ridiculed, mocked and ignored--because she has stated that immune cells are supposed to be in the brain to aid, repair and rebuild.  She has published on the premise that immune cells are neuroprotective.
link

Dr. Michal Schwartz of the Weizmann Institute of Science has questioned whether immune ablation and suppression  in multiple sclerosis drugs was the correct approach.  Her research showed that it was essential not to completely stop the immune cells entering the MS brain, but to retrain the cells:  immune modulation, rather than immune suppression.  She continued to publish that immune suppressing drugs had fallen short, that MS continued to progress.  She thought it was impossible that the brain would have given up its ability to be assisted by the immune system.  It simply did not make sense to her.  Why would our most important organ not need the immune cells?
link

Immune ablation and suppression never made sense to me.  Subsequently, I've been following her research ever since Jeff was diagnosed with MS in 2007.  And that's why Jeff has only ever been on Copaxone, which was developed at the Weizmann Institute.  Copaxone retrains the immune cells thought to be causing damage, and leaves the others intact.

Dr. Schwartz likes to quote Abraham Lincoln--
"If you are doing any revolution, do not try to convince your opponents,
if you are right, you don't need it.  If you are wrong, it will not help you."

Dr. Schwartz has been quietly conducting her revolution in Israel, publishing her research in medical journals, and speaking out on the absolute necessity of immune cells in the brain.  As she says, "A healthy mind depends on a healthy immune system."  These so-called lymphocyte "auto-immune cells", which MS drugs sought to inhibit, were the exact same ones her research showed were needed to repair the brain.  And she established her theory of "protective autoimmunity."  Her research continued to show that these cells were needed to create new stem cells.
link

Immune cell suppression and ablation will need to be reconsidered now.

She has been brave enough to keep on this trail.  And now, with the recent U of V research,  it appears she was right all along.
Here's Dr. Schwartz presenting her research in plain English.
Give her fifteen minutes of your time---listen to her revolution.
link


Be careful with serious immune ablating and suppressing drugs, especially while we're still learning about the function of immune cells in the CNS.  If this past week and the U of V research has taught us anything, it's that we simply don't know what we don't know...

be well, be hopeful,
be educated,

Joan