Increasing drainage to save the brain

Researchers at Keck's School of Medicine at USC are looking at a compound (Piezo1) which increases the diameter of lymphatic vessels which drain the brain of toxins and metabolites.  Dr. Young-Kwon Hong has discovered a potential breakthrough which may help those with diseases of neurodegeneration. 

Hong’s team theorized that they could speed up the draining of fluid and waste from the brain. “Think about a kitchen sink that’s draining too slowly because it has a two-inch pipe,” he said. “We can give you a four-inch pipe.” Hong and his team first developed the idea of manually stimulating the drainage process, and then they developed a compound that triggers an increase in the diameter of the lymphatic vessels. Hong’s research was published in Nature Neuroscience in March of this year, and he and his team continue to move forward with this exciting development.

https://keck.usc.edu/news/usc-researcher-discovers-drug-that-may-delay-onset-of-alzheimers-and-parkinsons-disease-and-treat-hydrocephalus/

Here is the published research in Nature.

Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation

https://www.nature.com/articles/s41593-024-01604-8

Adequate lymphatic drainage of the brain is essential for brain health. 

Here is a wonderful review of the research from Glasgow-- this area of study is just beginning, but there are links to be found in impaired (g)lymphatic drainage and MS.

https://www.sciencedirect.com/science/article/pii/S221103482400035X

Multiple sclerosis (MS) is a complex autoimmune disorder that affects the central nervous system, resulting in demyelination and an array of neurological manifestations. Recently, there has been significant scientific interest in the glymphatic system, which operates as a waste-clearance system for the brain. This article reviews the existing literature, and explores potential links between the glymphatic system and MS, shedding light on its evolving significance in the context of MS pathogenesis. The authors consider the pathophysiological implications of glymphatic dysfunction in MS, the impact of disrupted sleep on glymphatic function, and the bidirectional relationship between MS and sleep disturbances. By offering an understanding of the intricate interplay between the glymphatic system and MS, this review provides valuable insights which may lead to improved diagnostic techniques and more effective therapeutic interventions.

Vascular endothelial dysfunction associated with severity in MS

I wanted to provide a recent research round-up on the connection of MS to vascular health, specifically how endothelial dysfunction contributes to MS progression.  

As I've explained in another blog post, I do not feel it is appropriate for me to be dispensing medical advice as a layperson.  But I am still interested in seeing the exploration of the vascular connection to MS, and happy to share that the research continues. 

Jeff is now 15 years out from his MS diagnosis, and has shown no further MS disease progression.  His most recent MRI from last June shows continued healing of old lesions and completely healthy, normal gray matter.  And he's still composing, conducting, traveling, teaching, biking, jogging, living.  As his new GP recently commented, he's an incredibly healthy 59 year old man.  The fact that he has had MS for 15 years astonishes her.  Me too.

Here's a short research wrap up:

1. A group of Japanese neurologists examined the level of endothelial dysfunction exhibited by people with MS and found a correlation between lower flow mediated dilation (FMD), endothelial dysfunction, and MS progression.  FMD is lowered when we do not have enough endogenous nitric oxide.

Twenty-seven patients with MS and 24 healthy controls were enrolled. FMD was significantly lower in MS subjects than in control subjects (6.0 ± 0.6 vs. 8.6 ± 0.7, p = 0.006); furthermore, BHI was similarly lower in MS than in controls, but insignificant. Remarkably, FMD was significantly lower in secondary progressive MS subjects than in relapse-remitting MS subjects (3.7 ± 1.3 vs. 6.7 ± 0.7, p = 0.045). In addition, FMD was inversely correlated with the disability score as per the expanded disability status scale (R2 = 0.170, p = 0.033) and modified Rankin scale (R2 = 0.187, p = 0.027).

https://www.msard-journal.com/article/S2211-0348(21)00402-8/fulltext#%20

2. Russian neurologists are looking at how homocysteine decreases endothelial health, and contributes to MS progression. 

The effect of homocysteine on endothelial dysfunction was shown in vitro. It was reported that homocysteine (500 µM) decreases the viability and induces the apoptosis of human vascular endothelial cells. Increases in reactive oxygen species in endothelial cells treated with homocysteine were also found [70]. Increasing concentrations of reactive oxygen species in endothelial cells homocysteine may induce vascular inflammation [19,28]. 

https://www.mdpi.com/2076-3425/10/9/637/htm

I first wrote about the danger of elevated homocysteine levels as part of the Endothelial Health Program

Anemia/low vit. B12 creates high levels of homocysteine in the blood (a sulfur containing amino acid) which damages the endothelium A strict vegetarian diet that excludes all meat, fish, dairy and eggs, or an unbalanced diet of processed foods could create low vit. B12 levels and damage the endothelium (10)

https://ccsviinms.blogspot.com/2016/04/the-endothelial-health-program-8-years.html

3. Our friends from the ISNVD, Dr. Mark Haacke and Dr. Yulin Ge, continue to look at the MS brain, to study the vasculature.  This group is noting a new venous vascular sign in lesions, which they are calling multiple vessel sign (MVS).  Using a new contrast agent called Ferumoxytol, the researchers were able to see enhanced images of MS lesions, and noticedmany more small vessel abnormalities.  Rindfleisch's discovery of the dilated blood vessel, the central vein sign, continues to be explored.

 The total number of lesions with vascularity on pre- and post-contrast data were 287 and 488, respectively. The lesions with abnormal vascular behavior were broken up into following categories: small lesions appearing only at the vessel boundary; dilated vessels within the lesions; and developmental venous angiomas. These vessel abnormalities observed within lesions increased from 55 on pre-contrast data to 153 on post-contrast data. Finally, across all the patients, the periventricular lesional vessel density was significantly higher (p < 0.05) than that of the periventricular NAWM.

https://pubmed.ncbi.nlm.nih.gov/33338965/

4. And finally, here is a fabulously thorough review from the ISNVD 2020 meeting, published in 2021.  This paper can serve as a primer for any medical researcher interested in learning more about the vascular connection to MS.  It's all here.  

https://www.frontiersin.org/articles/10.3389/fneur.2021.561458/full

stay well,

Joan

Fabricated Alzheimer's research scandal

Two weeks ago, a scandal blew up the world of Alzheimer's disease research.  

Thanks to an investigative report at Science, it was revealed that slides of beta amyloid plaques attached to a 2006 research paper were enhanced and research fabricated, affecting a decade's worth of research and failed drug development, and undue agony for Alzheimer's patients and families.  I suggest reading this report, for all of the gory details.  

https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease

How could this happen?  Was it simply the pressures of academia to publish or perish?  Or pressures from pharmaceutical companies who fund research to find a profitable drug solution?  Could it be a myopic understanding of specific protein build up in the brain, without consideration of the underlying processes behind inflammation, slowed cerebral perfusion and drainage?  Was it due to the credo of neuroimmunologists which focuses on the trees, rather than the forest?  I would posit it is all of the above.

Readers of this blog know that I have written about the importance of understanding a systems approach to healing in diseases of neurodegeneration, including MS.  But a systems approach will never be one drug, pill, or infusion.  A systems approach can never be placebo trialled.  It will never make money for researchers of big pharma, so they won't fund studies.  And this is a problem.

In 2014, I  talked to ISNVD keynote speaker Dr. Paula Grammas regarding her Alzheimer's Disease research, which was focused on the multi-factorial causes of Alzheimer's related to vascular inflammation.  

https://www.youtube.com/watch?v=fIaPgxOC_4o

Below, I'll copy and paste a 2014 post on this topic, including the groundbreaking Alzheimer's research of Dr. Dale Bredesen. Dr. Bredesen had been concerned that a billion dollars of Alzheimer's research money was going to understanding beta amyloid plaques as a target for drug development.  Turns out, he had a lot of reason for his concern.  

 https://ccsviinms.blogspot.com/2014/10/systems-approach-to-healing-alzheimers.html

Published in the September issue of Aging, "Reversal of cognitive decline: A novel therapeutic program", a new study at UCLA shows exactly how a personalized "Systems Approach" helped Alzheimer's patients recover memory and health.

Dr. Dale Bredesen, Professor of Neurology at UCLA, authored the new paper.  Dr. Bredesen is one of many researchers who has questioned the pharmaceutical model of inhibiting beta amyloid plaques in Alzheimer's.  

In the case of Alzheimer's disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease's progression, and drugs have only had modest effects on symptoms. "In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer's at an aggregate cost of over a billion dollars, without success," he said.

The model of multiple targets and an imbalance in signaling runs contrary to the popular dogmathat Alzheimer's is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain -- as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer's disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.

http://www.sciencedaily.com/releases/2014/09/140930143446.htm?utm_source=feedburner

Dr. Bredesen believed that using a multiple target lifestyle therapy with his Alzheimer's patients might improve brain signaling.  Here are the main features of the program he created, which was adjusted for each individual patient.

(1) eliminating all simple carbohydrates (breads, pastas, baked goods)

(2) eliminating gluten and processed food, with increased vegetables, fruits, and non-farmed fish

(3) reducing stress with yoga
(4) as a second measure to reduce the stress, meditation for 20 minutes twice per day
(5) melatonin each night
(6) increasing sleep from 4-5 hours per night to 7-8 hours per night
(7) methylcobalamin (vitamin B12)
(8) vitamin D3

(9) omega 3 fish oil
(10) CoQ10 
(11) Exercising for a minimum of 30 minutes, 4-6 days per week.

(Long time readers of this blog will notice that this program shares a lot with the Endothelial Health Program)

http://ccsvi.org/index.php/helping-myself/endothelial-health

The results for 9 patients was better overall health, better body mass index, and a reversal of memory loss.   That's Alzheimer's Disease reversal!   Something no one drug has been able to achieve.

I've written about the difficulty in conducting double-blind, placebo control trials for lifestyle.   As Dr. Roy Swank, Dr. George Jelinek and Dr. Terry Wahls could all attest,  the "gold standard" trial approach works best for drugs. But that doesn't mean a holistic approach to healing is invalid, or cannot be trialled.  It just means it takes more work for both patient and researcher.  

There is no way to patent or monetize a new lifestyle, so drug companies won't be paying for these studies.   However, a holistic approach addresses many different aspects of health.

Yes, this is a small study, and yes, it is still anecdotal evidence.  But this program can be used in clinical trials.  It will be costly, and take time---but it may save brains.

What does this Alzheimer's research have to do with MS?  When we consider the link of the heart to the brain and the importance of cardiovascular health to cerebral perfusion, we can understand the need for endothelial health.  An oxygenated, perfused, cleansed and fed brain is a happy and healthy brain.

All diseases of neurodegeneration share hypoperfusion, or simply, reduced cerebral blood flow.  

http://ccsvi.org/index.php/the-basics/ccsvi-in-other-neurological-diseases

There are lifestyle changes that can be made to aid healing.  Please note that I did not use the word "cure."  For more on how the "cure mentality" can hamper our efforts to heal--read 

http://ccsviinms.blogspot.com/2014/06/the-cure-mentality.html 

The era of a "brain in isolation" research is ending.  More and more researchers, like Dr. Bredesen, are considering the body as a whole unit, and addressing cardiovascular function in brain health.

Thanks to Dr. Bredesen and UCLA for going up against the pharmaceutical companies, and bringing hope and healing to his Alzheimer's patients. 

Where are the MS specialists ready to take on this challenge?

We're waiting,

Joan