MS "breakthrough" research--On/Off Switch!!!

I am sick and tired of reading news stories about some "new MS breakthrough" which uses the EAE mouse model of MS and describes MS as an autoimmune disease.  It is as though the immunology research community believes that if they just keep acting like they are busy discovering things (where they have been looking for 70 years and finding nothing about disease etiology) they can keep getting funding for their labs, and keep people with MS thinking there is momentum.

The latest in a sea of sameness is the Bristol University crap about an "on/off switch" for the immune response to MS.

Here's the full paper, published in Nature---for those who like to read published research, rather than press releases full of hyperbole and BS.

http://www.nature.com/ncomms/2014/140903/ncomms5741/full/ncomms5741.html

In reading the paper, we learn that this new "breakthrough" is remarkebly reminiscent of Copaxone treatment, in which killer T cells are said to be modulated to helpful T cells by means of exposing them to an antigen (in Copaxone's case, that's a mimic of the proteins found in myelin basic protein---glatiramer acetate.)  This particular "new breakthrough hope"  therapy is going after CD4+ T cells, using injected peptide epitopes, rather than intact antigens--which are said to be "more effective."

Again, all of the testing was done on the mouse model, EAE.  Not humans with MS.

As reviewed elsewhere23, 45, peptide epitopes targeting ​CD4+ T cells have distinct advantages over intact antigens, and yet the mechanism by which peptide therapy prevents and treats ongoing autoimmune and allergic diseases is poorly defined. Mucosal routes of administration have proven safe and effective in animal models of allergy and autoimmunity, but have not translated well to the clinic. Here we demonstrate that the s.c. route of administration is more effective than the i.n. route, with a 1,000-fold lower dose of antigen being effective for anergy induction when compared with previous studies17, 18. As noted17, the efficacy of tolerance induction and disease prevention depends on signal strength. In this study, all aspects of inflammatory T-cell function, including proliferation, inflammatory cytokine secretion and encephalitogenicity were suppressed, whereas the ability of cells to secrete ​IL-10 and suppress EAE increased in a dose-dependent manner. ​IL-10 clearly serves as a promising mediator of effective antigen-specific immunotherapy1, 12.

But muting or changing the inflammatory response of CD4 + T Cells isn't really explaining why they are there in the first place, or how come this exact same cellular response shows up in ischemic stroke, slowed cerebral blood flow and reperfusion injury in humans.

That's right!!  CD4+ T cells show up after stroke, ischemia, and reperfusion injury.  These cells are responding to slowed blood flow in the brain, or hypoperfusion.

Here are stroke and vascular researchers discussing CD4+ T cells and the immune reaction to stroke and vascular issues in published research.  Perhaps we should let them know that stroke or reperfusion injury is an autoimmune disease that can be turned on or off!

For instance, lymphocytes from stroke survivors show more activity against myelin than the lymphocytes from patients with multiple sclerosis. In addition, myelin-reactive T cells are found in higher numbers among patients with cerebrovascular disease. These data thus provide evidence that a cellular immune response to brain antigens occurs following stroke.
http://stroke.ahajournals.org/content/41/10_suppl_1/S75.full


These findings indicate that CD4⁺ and CD8⁺ T lymphocytes, but not B lymphocytes, contribute to the inflammatory and thrombogenic responses, brain injury, and neurological deficit associated with experimental stroke
http://circ.ahajournals.org/content/113/17/2105.long

These findings implicate a CD4+ subset of T lymphocytes as key mediators of early inflammatory responses after renal  ischemic reperfusion  injury. 

http://www.scielo.br/pdf/bjmbr/v40n4/6420.pdf


I have a novel suggestion for researchers---why not look at the connection of MS to stroke, the vascular endothelium, CCSVI and reperfusion injury?  Why not understand this cellular response in non "auto-immune" diseases?

Now that would be a REAL breakthrough,
Joan

Understanding Endothelial Dysfunction--learning from Ebola crisis

The horrific outbreak of the Ebola virus in West Africa is causing researchers and physicians around the globe to ask what can be done to slow the death rates in this vulnerable population.

A recent piece in the New York Times, titled "Can Statins Help Treat Ebola?"  is authored by Dr. David S. Fedson, a retired professor of medicine at the University of Virginia.  Dr. Fedson writes about the current crisis of the Ebola epidemic and the short supply of life-saving drugs.  He suggests that there are other treatments, aside from experimental and expensive drugs, that have already been tested in humans, are readily available and can modify the body's response to the virus.

How would these drugs help?  They target endothelial dysfunction.

More than a decade ago, clinicians noted striking similarities between patients with Ebola and those with bacterial sepsis. Both diseases involve severe dysfunction of the endothelial cells that line blood vessels throughout the body. This dysfunction in turn precipitates major abnormalities in blood coagulation. Both can eventually lead to the failure of internal organs, primarily the liver and kidneys, and organ failure often leads to death. 

Researchers have since discovered that abnormalities of endothelial function and coagulation can be modified or reversed by treatment with drugs such as statins, angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), which were developed to treat patients with cardiovascular diseases and diabetes. 
http://www.nytimes.com/2014/08/16/opinion/can-statins-help-treat-ebola.html?_r=1

Dr. Fedson suggests that strengthening the endothelium with cardiovascular drugs may be the key to stopping organ failure and saving lives in the Ebola outbreak.

These very same statins have been suggested as a treatment for secondary progressive multiple sclerosis, as they reduced brain atrophy (from 0.6% to 0.3% per year) in pwMS when compared to placebo.  MS doctors are more accepting of a pill, rather than life-style modification, when treating disease, as a pill can be placebo-controlled and trialled.  And they most certainly never explain why cardiovascular treatments might slow brain atrophy.  But as we have all learned, it's because of blood flow to the brain.
http://www.sciencedaily.com/releases/2014/03/140318190031.htm

In fact, all of the above mentioned cardiovascular drug treatments are now being tested in people with MS, to slow down neurodegeneration and brain atrophy; death of brain tissue due to endothelial dysfunction.  These drugs are not immune modulating---rather, they address blood flow, endothelial function and coagulation.  Here's more on the new medications being tested in MS.
http://ccsviinms.blogspot.com/2013/08/medications-for-ms-addressing-blood.html

What can those with a chronic and progressive disease like MS take away from this deadly Ebola outbreak?   There is a vascular connection to this terrible disease, as there is a vascular connection to MS.  A strong endothelium is the body's best defense.  Keeping the blood vessel lining healthy and impermeable is the surest way to maintain cerebral circulation for those with MS.   Endothelial health will slow brain atrophy and may even reverse it.

But you don't need a statin.  There is much that can be done with lifestyle, nutrition, and exercise.
http://ccsvi.org/index.php/helping-myself/endothelial-health

Here's to more healing ahead!
Joan

Inadequate cerebral blood flow and loss of neurons in MS

A new study was recently been published in the JAMA Neurology journal.  One of the investigators is Yulin Ge, MD--a recent presenter at the International Society for Neurovascular Disease conference.  www.isnvd.org  Dr. Ge has been imaging the MS brain for over a decade at NYU, and he has found many vascular connections to MS.

The study looks at cerebrovascular reactivity, or CVR.  CVR is how the brain reacts or responds  with blood flow when there is vasodilation.  This function is extremely important, as neurons need adequate blood flow to provide glucose and oxygenation.  Without this response of adequate cerebral bloodflow (CBF), the brain will not function properly, and neurons can potentially die.

http://archneur.jamanetwork.com/article.aspx?articleid=1893478

What this new study did to measure CVR was to look at how healthy controls and pwMS responded to a hypercapnia (too much carbon dioxide), which the researchers created by using 5% carbon dioxide gas.  This gas increases cerebral blood flow by creating vasodilation--or a widening of blood vessels.  A healthy endothelium (lining of the blood vessels) would normally respond to hypercapnia by widening vessels and allowing for more blood to flow to the brain.

Patients with MS had a significant decrease of cerebrovascular reactivity compared with controls. This decrease in CRV correlated to gray matter atrophy, but did not correlate with white matter lesions. 

Their conclusion was that there is an impairment in the cerebrovascular pathophysiology in pwMS, and that inadequate blood flow to neurons may indeed be the cause of neurodegeneration in MS.  And that this was a vascular problem, NOT a problem initiated by white matter lesions.

We know that impaired CVR is related to arterial stenosis and occlusion of the blood vessels in the neck.  http://www.hindawi.com/journals/rrp/2012/268483/

Note that this new study did not hypothesize why this is happening in people with MS. But this study could well be related to what the Columbia researchers saw when they damaged the vascular endothelial cells outside the brain.

The Columbia University study, which was published earlier this summer, found that when researchers damaged the vascular endothelial cells lining the blood vessels outside the brain using lasers to cause oxidative stress,  they could disrupt blood flow to the brain and affect neurovascular coupling.  http://ccsviinms.blogspot.com/2014/06/columbia-researchers-provide-new.html

Dr. Zamboni has noted that there is a derangement of the endothelial cell layer in the jugular veins and valves in people with CCSVI/MS.  This loss of endothelial cell integrity could well be causing the decrease in cerebrovascular reactivity seen in people with MS.
http://phl.sagepub.com/content/early/2014/06/27/0268355514541980.abstract

As an anecdotal side note, my husband's gray matter atrophy reversed after he was treated for dural and jugular venous stenosis and began following the Endothelial Health Program.
http://ccsvi.org/index.php/helping-myself/endothelial-health
And he has had no further MS progression since 2007.

The heart and brain are connected, and a healthy endothelium is essential to both.
Something to consider,
Joan