Welcome! This blog contains research, information on lifestyle, nutrition, dietary supplements and health for those with MS, as well as continuing information on the understanding of CCSVI and cerebral hypoperfusion. This blog is informative only--all medical decisions should be discussed with your own physicians.

The posts are searchable---simply type in your topic of interest in the search box at the top left.

Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the immune paradigm of MS, and continues the 15 billion dollar a year MS treatment industry. But as we learn more about slowed blood flow, gray matter atrophy, and environmental links to MS progression and disability--all things the current drugs do not address--we're discovering more about how to help those with MS.

To learn how this journey began, read my first post from August, 2009. Be well! Joan

Thursday, June 16, 2016

Cerebral Microbleeds and MS




Readers of this blog will know I began writing about the vascular connection to MS after finding a link between Jeff's hypercoagulated serum test results, the small dots of blood seen on his legs called petechiae, and the realization that if he had pinpoint drops of blood escaping vessels on his legs, this could be happening in his brain, as well.  Blood in brain tissue creates oxidative stress, causes demyelination and initiates the coagulation cascade.  Dr. Roy Swank had noted the same thing in the 1950s, and had termed the leaky vessels "fragile capillaries."  I brought this research into the 21st century, by linking this blood vessel fragility to endothelial dysfunction and issues with nitric oxide.
Link

Finally, neurological researchers are noting the importance of cerebral microbleeds in the brains of those with MS, and exploring the cardiovascular connection to MS progression.

Published online today in Radiology, BNAC at the Jacobs School of Medicine in Buffalo reports on the link of cerebral microbleeds to disability in patients with MS.  link

The researchers found that the more cerebral microbleeds a patient had, the more severe were their physical and cognitive outcomes. In particular, MS patients who had more cerebral microbleeds had more physical disability after adjusting for age, hypertension and whole-brain volume.

"This is significant because it suggests that cerebral microbleeds are associated with increased physical disability in MS patients, independent from these additional risk factors for cerebral microbleeds," said Zivadinov.

In terms of cognitive disability, the researchers found that in the subgroup of MS patients who underwent neuropsychological testing, those with more cerebral microbleeds had higher disability on verbal and other cognitive function tests.

"Those MS patients who have cerebral microbleeds are subject to developing more physical and cognitive disabilities earlier in their disease, and therefore monitoring them more closely might be appropriate," Zivadinov noted. 


Significant research is now being done on ways to combat cerebral microbleeds, Zivadinov said, adding that currently, prevention of cardiovascular risk factors was seen as the best way to prevent their formation since there are no currently available target therapies.


This is exactly why taking care of heart health is so vitally important.  There are NO DRUGS to prevent cerebral microbleeds.  It is why I created the Endothelial Health Program to combat all of the environmental factors which contribute to the weakening of the endothelial cells.  A strong endothelium keeps blood inside vessels and stops micro bleeds.  It's not a pill, it's a lifestyle.

The heart and brain are connected, and the research keeps coming in to prove this.  I look forward to the day when cardiovascular and endothelial preserving therapies are the FIRST LINE treatment recommended to MS patients.

Joan







Wednesday, June 1, 2016

Gene implicated in progressive MS related to vascular disease

New research published in Neuron by the University of British Columbia finds an inherited genetic mutation related to rapidly progressing MS (PPMS).  link Variants of the mutation are also seen in inflammatory vascular diseases.   This research was first presented at ECTRIMS in 2015 link

The mutation of gene NR1H3 was found in seven of 2,000+ people with MS,  and 70% of the people with this mutation went on to develop MS.   Blood samples with this mutation were taken from two Canadian families who have members with primary progressive MS.  Although this mutation is rare,  it could an important marker for those diagnosed with PPMS, and help scientists understand the disease process behind PPMS.

This discovery relates to inflammation, lipids, and vascular health, as the NR1H3 gene encodes liver receptor protein A (LXRA)  If there is a mutation,  liver receptor proteins are dysregulated, lipids cannot be processed and inflammation occurs. But the UBC press release doesn't even mention this.

Cardiovascular researchers have found an NR1H3 mutation related to vascular inflammation, coronary artery disease, diabetes, metabolic disease, and serum lipid processing.
link  link 

Alzheimer's researchers have found an NR1H3 mutation related to AD disease severity.

And stroke researchers are studying how this is related to ischemic vascular disease. 

How does this genetic mutation affect the vascular system in all of these different diseases?  It's all about inflammation and fats.

Liver X receptor  (LXR) proteins are mainly found in the liver and adipose, or fat tissue.  They help the body process fats and cholesterol.  link  
In obese patients, there is an increased release of free fatty acids, and this can lead to liver disease, inflammation, metabolic diseases and diabetes due to LXR protein dysregulation. 
link  link  link
LXR proteins are expressed on endothelial cells and in adipose (fat) tissue, and affect the inflammatory response.
Cardiovascular exercise creates laminar flow and shear stress over endothelial cells, and this regulates LXR proteins, decreasing inflammation.  link


Now, understanding this information,   here is Dr. Traboulsee on this discovery of an NR1H3 mutation in MS-

“If you have this gene, chances are you will develop MS and rapidly deteriorate,” said co-author Dr. Anthony Traboulsee, the MS Society of Canada Research Chair at UBC and Director of Vancouver Coastal Health’s MS and Neuromyelitis Optica Clinic. “This could give us a critical early window of opportunity to throw everything at the disease, to try to stop it or slow it. Until now, we didn’t have much basis for doing that.”   link

What would part of this critical early window,  "throw everything" treatment be?

A treatment program for someone with an NR1H3 genetic mutation--as we understand it in currently modeled studies of variants (link and link
  
1. stop eating a high fat/high glucose/low nutrient "western style diet"  
2. regulate fat intake by avoiding known inflammatory fats and increasing anti- inflammatory omega 3 fats,  
3. increase anti-oxidants and fiber from fruits and vegetables,  
4. eliminate excess sugar and processed foods,  
5. maintain a healthy body weight through optimal nutrition and exercise.  


All of the above lifestyle interventions help counteract the influence of dysregulated LXR proteins by limiting damaging fats, decreasing inflammation, and strengthening the vascular endothelium; giving  the heart, liver and brain their healthiest environment.   It will not change the genetic mutation, but it can help modify and calm the body's inflammatory response.  Today.   link

Sounds a lot like what Dr. Roy Swank was publishing sixty years ago.      link

Do you truly want to "throw everything" at this disease, and stop and slow MS progression, Dr. Traboulsee?  Really?
Because there has been an incredible amount of research recently pointing to food and MS progression.  The western diet harms the microbiome and increases inflammation link  link
and fasting reduces inflammation. link
In fact, your own colleague at UBC, Dr. Helen Tremlett,  recently published on the inflammatory gut microbiota associated with children with MS.  link

Let's get this information out and help people now.



Joan


Sunday, May 15, 2016

Ocrelizumab and "wrapping up MS"

While Dr. Stephen Hauser is proclaiming the "spectacular" results of the latest immune cell suppressing therapy, ocrelizumab, other MS researchers are not as impressed.  link

In a press release full of bravado and hyperbole---"Wrapping up multiple sclerosis at UCSF"--  link  Dr. Hauser humble brags about his discovery.

“My hope is that, with these wonderful results against relapsing MS and finally a treatment that works at least partially for PPMS, there will be new octane in academia and industry to make even more meaningful advances,” says Hauser. “MS is no longer a black box. There is so much more that can be accomplished, and we need to build upon this important success.”

Hauser's wording could not be more ironic----as there will most likely be an FDA black box warning for ocrelizumab, due to the risk of deadly infections, malignancies, and patient deaths.

Dr. Thrower predicted that the FDA may approve ocrelizumab with a black box warning for progressive multifocal leukoencephalopathy (PML)
link

But Montalban noted that there were numerically more malignancies among those in the drug group. There were 11 cancers among those on ocrelizumab compared with only two in the placebo group, something that deserves further monitoring, he said.  There was also a numerical imbalance in deaths, with four in the drug group and one in the placebo group.
link


Ocrelizumab is a CD20 monoclonal antibody,  which was originally developed as a lymphoma treatment.  It targets and binds mature B lymphocytes and suppresses them.   It is a humanized version of the chimeric Rituxan, (which was a the end of its patent and had to be altered and re-patented for MS, to continue making money.)  So, the idea that this is a new discovery could not be further from the truth.

In fact, ocrelizumab has been around for many years, and trials of this drug in rheumatoid arthritis and lupus were halted, after serious infections and deaths were reported at 52 and 48 weeks.

There were 6 deaths associated with serious infections in the RA phase III trial.
link
There were 5 deaths associated with serious infections in the Lupus phase III trial.
link

The financial press didn't think ocrelizumab would ever get this far. The Wall Street Journal commented on the dangers of the drug back in 2010, when Roche ended its RA drug trial.

"Roche said Tuesday that ocrelizumab's phase II trials in treating patients with relapsing remitting multiple sclerosis are continuing. But some analysts doubt the drug will come to market as the recent safety issues are likely to put the U.S. Food and Drug Administration on alert.

The recent trial failures have curbed the drug's sales potential and some analysts now expect that if ocrelizumab's multiple sclerosis indication passes all regulatory hurdles, it will generate less than $1 billion in annual sales."

Another problem is that autoreactive B cells return after treatment termination, as this study of rituxan in type 1 diabetes illustrated.  Autoreactive B cells would create a rebound or relapse after the immune system is reconstituted, similar to what we see with the Tysabri immune reconstitution inflammatory syndrome (IRIS), which occurs after termination of treatment.

We conclude that anti-B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti-B cell therapy.

If MS researchers truly want to make breakthrough discoveries, they will have to expand past the EAE mouse model and their narrative of the out of control immune system.  They could begin by looking at the the newly discovered lymphatic vessels of the CNS, cerebral endothelial cell permeability,  fibrinogen, microbleeds in the MS brain, neurodegeneration and hypoperfusion. If plasmic particles, like viruses, are indeed entering the MS brain through a permeable blood brain barrier, than blocking B cells may not be the best idea.  Time will tell.

So much for "wrapping up" MS.....in a billion dollar black box. 
Joan