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

Medications for MS: addressing blood flow

August 22, 2013 at 12:16pm

With the growth of research into the connection of MS to cerebral blood flow,  we've seen an interest in exploring new ways to address hypoperfusion (slowed blood flow), endothelial dysfunction (damaged blood vessels) and  brain atrophy (loss of brain tissue).

Why is this?  Because MS specialists, neurologists and advocacy groups are much more comfortable designing, testing and recommending a drug for MS, rather than encouraging healthy lifestyles and treating venous malformations.  You cannot monetize or patent a diet, exercise and angioplasty.  It's impossible to have a placebo-controlled clinical trial for lifestyle.  But you can develop a drug and make a lot of money selling it to a population with a chronic and degenerative disease.  

Please note that I am not recommending these specific drugs at all, I'm just pointing out how MS research is slowly shifting.  

We saw this paradigm change happen with the Vitamin D.  Six years ago, Jeff's neuro chuckled when I asked to have his D3 levels tested. But slowly, with independent research funded by patient advocacy groups like Direct MS,  the research paradigm has changed. And now, neurologists are testing their new patients' vitamin D levels, and adding supplementation accordingly. I believe we will see this shift continue with drug approaches to reducing hypoperfusion. 

This is tacet proof that blood flow matters in MS.  But you will not hear that from neurologists-yet.   They will discuss cerebral blood flow with their patients when they have a prescription they can write.  

Here's some info on a few of these new medications which target blood flow, currently in clinical trials.

Ibudilast (MN-166)

Clinical trials in progressive MS patients to be lead by Dr. Robert Fox and the Cleveland Clinic with the NMSS.  Dr. Fox received NMSS money to study CCSVI, and after finding new venous malformations in the jugular veins of people with MS, he has moved on to a clinical trial using a vasodilating and neuroprotective drug.  Is this coincidental?

http://finance.yahoo.com/news/medicinova-announces-initiation-cooperative-phase-230000864.html

MN-166 has been marketed in Japan and Korea since 1989 to treat cerebrovascular disorders, including post-stroke complications, and bronchial asthma. MediciNova licensed MN-166 (ibudilast), from Kyorin Pharmaceutical for potential utility in MS.

Lisinopril 

An inexpensive blood pressure medication and ACE inhibitor which modulates angiotensin.  This drug opens up blood vessels and allows blood to flow more easily. This older drug is being developed to treat MS by Dr. Lawrence Steinman of Stanford University School of Medicine.  (Dr. Steinman is also one of the inventors of Tysabri--which he has since spoken out against as a first line treatment for MS.) 

... angiotensin immediately causes blood vessels to constrict. “That raises your blood pressure so when you stand up to get out of a chair, you don’t fall down and faint,” said Steinman, who is also the George A. Zimmerman Professor in the medical school. But angiotensin overactivity causes chronic hypertension. Lisinopril controls blood pressure by blocking an enzyme that converts angiotensin’s precursor into the active hormone. The drug also appears to have certain anti-inflammatory properties.

http://med.stanford.edu/ism/2009/august/lisinopril.html

Here is info on the current study:

 In these studies, lisinopril reduced molecular measures of inflammation that accompany MS, yet it did not inhibit overall immune function.

link 

Statins

Although these cholesterol-lowering drugs failed in earlier trials for RRMS, they are now being brought back to life to address brain atrophy in progressive MS.