BDNF, exercise and the vascular endothelium

Another new paper showing the vascular connection to MS.

New research shows that a 24 week resistance and endurance exercise program increases brain derived neurotrophic factor (BDNF) in people with MS.
link

At baseline, the BDNF concentration of persons with RRMS was 21% lower than healthy controls. Following 24 weeks of intervention, changes in BDNF concentrations differed significantly between exercise group and sedentary group.  In particular, within exercise group, BDNF concentrations increased 13.9% ± 8.8%, whereas it decreased 10.5% ± 4.1% within sendentary group. 

BDNF is called the "Miracle-Gro" for the brain.  It is a very important cerebrovascular protein which protects neurons and allows for neurogenesis, or the growth of new neurons.  BDNF is vital to learning, memory and executive function.

Lower levels of BDNF are linked to Alzheimer's, dementia, depression, diabetes---and now, Multiple Sclerosis.

Cardiovascular researchers have known that exercise increases BDNF levels for quite some time.  Why?  Because BDNF is created by healthy vascular endothelial cells.  Cardiovascular health allows for BDNF creation.  How?  Shear stress--which is caused by blood flow over the lining of our blood vessels--activates the endothelium, and allows for BDNF secretion.
An active, moving body with an active, pumping heart is essential to the brain.
link

When will the tipping point occur?  When will MS specialists refer to the vascular connection to Multiple Sclerosis and begin to look at the endothelium?  When will they prescribe cardiovascular fitness to their patients?   When will they change the dialogue, to include heart health?

Still waiting for them---but you don't have to.
Move as much as you are able.  Incorporate an exercise program, and increase your own BDNF levels today.

Joan

 

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

Turf War

If all you read are neurological journals, you would assume CCSVI research is over and done. But CCSVI venoplasty studies are continually being published in peer-reviewed vascular journals---and the results are encouraging.


Here is a recent study from a university cardiovascular disease center, published this month in the Journal of Cardiovascular Interventions--looking at quality of life (QOL) one year after treatment to relieve venous stenosis.

Does an Endovascular Procedure Improve the Quality of Life in Patients with Multiple Sclerosis
http://interventions.onlinejacc.org/article.aspx?articleid=2492262

There were 94 MS patients tested for CCSVI (22 RRMS, 44SPMS and 26PPMS). 2 patients did not present with any vascular abnormality (that's 2%) and were not treated. Most patients had left IJV stenosis. The more disabled patients were, the more areas of venous abnormalities which needed treatment. The remaining 92 patients were all treated with balloon venoplasty.

By treating the venous abnormalities, cerebral venous drainage was increased.

There was a reduction in bladder disfunction, reduction in fatigue, improvement in disability and QOL for all of the treated patients, and these 4 parameters were maintained a year after treatment.There are other papers showing similar positive results after treatment. You will note that most are published in vascular journals, because this is a vascular treatment for a vascular problem.

Here are the some of the most recent ones on successful treatment for CCSVI:

http://www.ncbi.nlm.nih.gov/pubmed/24531803
http://www.pagepressjournals.org/index.php/vl/article/view/vl.2014.3854
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061177/
http://www.ncbi.nlm.nih.gov/pubmed/24806325


+++++++++++++++++++++++++++++++++++++++++++++++++++++

Why don't we hear about these published CCSVI studies? Primarily because MS immune modulating drugs are a $20 billion dollar a year business.  Yes, that's $20 BILLION dollars....with a B.   And this kind of money has created a disastrous turf war.
The value of the multiple sclerosis therapeutics market will rise slowly from $17.2 billion in 2014 to approximately $20 billion by 2024, at a Compound Annual Growth Rate (CAGR) of 1.5%, according to research and consulting firm GlobalData.
http://www.fiercepharma.com/press-releases/multiple-sclerosis-treatment-market-value-reach-20-billion-2024-says-global-0


We have known about this dilemma in medical research for decades. Vascular departments at universities simply do not receive the grant and pharma funding which is readily available to neuroimmulogical departments for drug development.  This has lead to an imbalance of power, and a betrayal of multiple sclerosis patients.


Read "Social constructionism and medical sociology: a study of the vascular theory of multiple sclerosis" a paper specifically addressing this divide, which was published in 1988.

http://onlinelibrary.wiley.com/doi/10.1111/1467-9566.ep11340153/abstract


brief excerpts below:


"A recent debate surrounding the pathogenesis of multiple sclerosis is analysed in terms of the skills, interests and backgrounds of the medical personnel involved. It is noted that the proponents of the vascular theory possess developed expertises in interpreting disease in structural, vascular terms, whereas their opponents' skills lie in immunology or neurology. Different observers have produced different conceptions of the disease because modes of observation, and the points from which observation takes place, differ. It is also noted that the debate over the causation and treatment of MS has occurred between a large and powerful social group (neurology) and a weak and marginal one (vascular specialists). The effects of this power inequality on the production an assessment of knowledge about MS are investigated. "


The paper goes on to discuss the very real turf war between vascular researchers and neuroimmunologists:

VASCULAR:

"Support for the idea of early vascular involvement in the aetiology of MS has also come from researchers working with the tomographic scanner. One of the standard techniques used in sectional radiography is a process whereby a radio-opaque dye is injected into the bloodstream, thus enabling any leakage through the walls of the blood-vessels to be readily observed. In other words tomographers possess well-developed skills in the study of lesion events within the vascular system. When these skills have been applied to the investigation of MS they have revealed fresh vascular features. "

"The dominant anatomic feature of multiple sclerosis is the relation of plaques to the venous component of the vascular system. The plaques, at least in the early stages, are almost always perivenular, extending as slender sleeves of demyelination. "


VS. NEUROLOGY:

"Furthermore, the clinicians who treat MS patients have always been neurologists - who tend routinely to conceive of MS as being essentially, as well as symptomatically, a neurological disorder.

Also the therapeutic implications of the auto-immune theory are generally pharmacological - involving modes of treatment with which most neurologists are already very familiar and in which they possess developed skills. A new drug treatment for MS, even the trial of a new drug, could be accommodated into existing clinical routines with little difficulty."



It is now almost 30 years since this paper was written. And very little has changed in mainstream MS treatments.
Not since Dr. Zamboni's discovery of CCSVI, Dr. Michal Schwartz's discovery of the brain's protective immune system, Dr. Jonathan Kipnis' discovery of the brain's lymphatic vessels which rely on veins, The Gladstone Institute's revelation that a singular drop of blood in brain tissue creates MS lesions, or Dr. Yulin Ge's visualization of microbleeds in the MS brain with 7T MRI.


The vascular connection to MS is still being swept under a very large $20 billion dollar rug.
MS has a quantifiable vascular component. However, I'm not planning on blogging about this for 20 more years.  Jeff's doing well, now nine years past an MS diagnosis with no disease progression. He has returned to his performing and conducting, as well as increasing his compositional output. We've been traveling the world, and enjoying his renewed health and vigor. His brain is healthier than it was when he was diagnosed with MS in 2007 and treated for CCSVI in 2009---with a reversal of gray matter atrophy and remyelination of his cervical lesion documented on MRI.

He is very fortunate, and he is not alone.

Let's hope that all of us, working together, can change MS research and treatment.

Coming up---information on an opportunity to donate to CCSVI Alliance's matching donation drive, and double your dollars to fund neurovascular research.


Joan