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.

link

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

link

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