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

Chemotherapy causes brain atrophy, demyelination and MS disease progression

While many MS specialists continue to explore chemotherapies and immunoablation for people with MS, the side effects of these drugs on the brain are rarely mentioned.

As we learn more about the long term effects of chemotherapy of the central nervous system, it is vitally important that people with MS are given the facts.

If you are being recommended to try any of these therapies, please discuss the side effects with your doctor.

Recent studies have now started to unravel the cell‑biological basis for commonly seen neurotoxic syndromes in chemotherapy associated central nervous system damage and have provided compelling explanations for delayed neurological complications, such as cognitive decline, progressive myelin disruption and brain atrophy.
http://www.ncbi.nlm.nih.gov/pubmed/20738009

1. Chemotherapy kills myelin and OPC cells--  Chemotherapies are known to affect healthy brain cells, causing them to die off long after treatment ends.   Studies have shown that months after exposure to common chemotherapies, oligodendrocytes and precursor cells continue to die, and the brain is unable to remyelinate.

This study is the first model of a delayed degeneration syndrome that involves a global disruption of the myelin-forming cells that are essential for normal neuronal function,” said Mark Noble, Ph.D., director of the University of Rochester Stem Cell and Regenerative Medicine Institute and senior author of the study. “Because of our growing knowledge of stem cells and their biology, we can now begin to understand and define the molecular mechanisms behind the cognitive difficulties that linger and worsen in a significant number of cancer patients.”
http://www.urmc.rochester.edu/news/story/index.cfm?id=1963

2. Chemotherapy changes the brain's metabolism--  Doctors have long-described "chemo brain"--a common and debilitating side effect of chemotherapy, causing cognitive fog and a loss of coping skills.  In fact, the brain's metabolism is altered.

Chemo brain phenomenon is more than a feeling. It is not depression. It is a change in brain function observable on PET/CT brain imaging."
With the help of special software, they were able to pinpoint differences in brain metabolism before and after chemo. They then correlated these with patient history and data from neurologic exams and chemo treatments.  The analysis reveals a statistically significant link between reductions in regional brain metabolism and symptoms of chemo brain.  Lagos says their findings show "there are specific areas of the brain that use less energy following chemotherapy".

"These brain areas are the ones known to be responsible for planning and prioritizing," she adds.
http://www.medicalnewstoday.com/articles/253277.php

3. Chemotherapy used in bone marrow transplant doubles brain atrophy in those with progressive MS.    Because of this, one neurologist is now cautioning his progressive MS patients.  The chemotherapy used in bone marrow transplant is likely to accelerate the disease progression in those with progressive MS.

The following study I was involved shows that when SPMSers are given chemotherapy they undergo increased neuronal loss, which is associated with faster progression on the EDSS and greater brain atrophy. The data speaks for itself. The picture below is what we call a survival curve of EDSS progressions and you can see that the MSers who had high serum levels of the neuronal toxicity marker neurofilament were much more likely to progress than those who did not have raised neurofilament levels. Similarly, brain atrophy rates in SPMSers were in the order of 2.1% per year in those who had a BMT compared to only 1.2% per year in SPMSers who did not have a BMT; the upper limit of normal for brain atrophy in healthy adults is generally accepted to be 0.4% per year. The bottom line is that if you have SPMS BMT is likely to accelerate your disease progression.
http://multiple-sclerosis-research.blogspot.com/2014/02/more-on-bmt-neurotoxicity-and-brain.html

4. Current information on Lemtrada (Campath/Alemtuzumab)
New claims are that treatment reduced cerebral atrophy in RRMS patients who were followed for two years---but earlier studies showed that this was not true in secondary progressive MS.  Treated patients were followed for 14 years past infusions---and cerebral atrophy and disease progression continued.  The FDA was right to deny Lemtrada in the US---sadly, the MS patients that are asking for this treatment to be approved have been given an incomplete scenario.

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. This particular group of patients who showed continuing disease progression had the highest inflammatory load prior to commencing alemtuzumab therapy. This group of patients were followed up with MRI scanning many years later (14 years post treatment) and did not demonstrate any increase in lesion load but did demonstrate further cerebral atrophy [Coles et al. 2006]. This was reflected in their EDSS score, the median being 7.5 (range 4.5–9) at latest follow up [Hill-Cawthorne et al. 2012].
http://europepmc.org/articles/PMC3629751

Campath 1H treatment was associated with a sustained and marked reduction in the volume of Gd enhancement, indicating suppression of active inflammation. Nevertheless, many patients developed increasing brain and spinal cord atrophy, T1 hypointensity, and disability. 
http://www.ncbi.nlm.nih.gov/pubmed/10489036



In fact, neurologists have known about chemotherapy causing brain atrophy for many years.  Here is a study from 2006--where neurologists followed brain atrophy after chemotherapy in preparation for a bone marrow transplant.  And they included a man without MS, being treated for cancer, to see how his brain did.  His brain atrophy doubled....just like the people with MS.

The man with non-Hodgkin lymphoma provided a clue. Because he didn't have MS, he should not have had any cerebral inflammation or edema. Yet, in the three months after he received the same treatment as the MS patients, his brain shrank at the rate of about 6 percent per year, a rate of atrophy similar to the MS patients.
http://journals.lww.com/neurotodayonline/Fulltext/2006/07040/Brain_Atrophy_in_Ms_May_Result_From_Immunoablation.11.aspx

We still do not fully understand the disease mechanism of MS.  While MS specialists continue to operate under the assumption that a faulty immune system must be annihilated ----we are learning that the true progression of MS can be linked to neuronal loss, or brain atrophy.  There is a terrible and tragic irony in the fact that chemotherapies, which are known to double brain atrophy rates, are being recommended to people with MS.

Please, share this information in the MS community.  For those who have already been treated with chemotherapies, there is hope of healing through diets high in antioxidants and phytonutrients and omega 3 oil supplementation. In fact, simple lifestyle factors like diet, exercise, UV rays and vitamin D are increasing blood flow to the brain are helping reverse brain atrophy in all of those with MS.

Know the facts, and be well,
Joan