"Neuroprotection" and Ibudilast

The latest MS drug trials all have a new target.  The new buzzword in MS drug development is "neuroprotection."  What does this mean, and why the switch?

Neuroprotection simply means protecting neurons by reestablishing blood flow and perfusion after a loss of oxygen to the brain.  We see these drugs are currently marketed to those who suffer from stroke.

Neuroprotective agents are used in an attempt to save ischemic neurons in the brain from irreversible injury.^[2]    http://emedicine.medscape.com/article/1161422-overview

I wrote about this subtle shift from drugs which modulate the immune system to drugs which address blood flow in 2013.  Here's that post:
http://ccsviinms.blogspot.com/2013/08/medications-for-ms-addressing-blood.html

What MS researchers are now doing is working with pharmaceutical companies to test and prescribe new drugs which address the damage caused by slowed blood flow.  And these drugs are called "neuroprotective."

Which is exactly what Dr.  Robert Fox is doing now with Ibudilast.

How does ibudilast work?   

It relaxes blood vessels and increases blood flow by inhibiting phosphodiesterases and releasing nitric oxide from the endothelium.

http://www.ncbi.nlm.nih.gov/pubmed/11607039

Dr. Fox has been working on a clinical trial for those with progressive MS, using Ibudilast (MN-166) which has been prescribed to treat stroke and asthma patients for two decades-

http://multiplesclerosisnewstoday.com/2015/05/13/major-progressive-ms-trial-completes-enrollment-experimental-therapy/

Ironically, ibudiblast has already been studied in a phase II trial involving 292 patients with relapsing MS and was found to decrease relapses.

However, Dr. Fox's trial will only be looking at progressive MS.  This way, people with relapsing remitting MS can still be sold expensive immune modulating drugs, and the researchers do not have to change their EAE story line.  

When Dr. Zamboni discovered the link to slowed venous return, hypoperfusion and MS, he opened up a new way of looking at the MS disease process.  Although neurologists and MS specialists will not say this, he has changed how they are studying the MS disease process and how they are developing drugs to treat MS.

And, not coincidently, one such researcher is Dr. Robert Fox.  In 2010,  Dr. Fox, a neurologist, received money from the MS Society to study CCSVI, a vascular disorder.   A medical student in his lab discovered never before seen venous malformations in the jugular veins of cadavers of people with MS.  And in 2011, the results of this study cause quite a stir at ECTRIMS.

Some results from the first 13 cadavers were presented during a platform session at ECTRIMS by Case Western University medical student Claudiu Diaconu. He confirmed that venous structures in the brain and brainstem appear to be far more complicated and variable than previously thought.

In fact, the postmortem study revealed the presence of a novel venous valve that had not been described in anatomy textbooks.

Perhaps the most important finding was that most of the stenoses identified in the study were not associated with vessel wall thickness or circumference.

As a result, Diaconu said, cerebrospinal vein scans in live patients "should focus on identifying intraluminal abnormalities, not just vessel wall narrowing or thickening.

http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/29266

What Diaconu found, and Dr. Fox knows---"intraluminal abnormalities with possible hemodynamic consequences were higher in MS patients compared to healthy controls."  
http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=137778&XNSPRACHE_ID=2&XNKONGRESS_ID=150&XNMASKEN_ID=900

"Hemodynamic consequences from intraluminal abnormalities" simply means they found a mechanical reason for the slowed blood flow, also known as hypoperfusion, which exists in MS.  Blockages inside the veins.

This hypoperfusion and ischemia in MS is a fact.  But neurologists and MS specialists cannot make any money treating venous malformations, or understanding how to improve perfusion with nutrition, exercise and lifestyle adjustments.  Understanding the heart brain connection won't benefit them, or their labs.

That's right.  Dr. Robert Fox will never tell you that ibudilast is a post stroke treatment, already approved and shown to relax blood vessels, increase blood flow, oxygenation and perfusion in the brain.  And it helps people with RRMS, as well as progressive MS.  He will tell you it is "neuroprotective" and blood flow doesn't matter....

I am so sick and tired of this charade.  I hope everyone can understand this.  Medicalese is being used to keep people in the dark regarding the MS disease mechnisms.

Hypoperfusion and slowed blood flow are realities in MS.  

Make sense?

Joan

Dr. Fox's and Cleveland Clinic CCSVI study update

July 14, 2011 at 1:52pm

The one year update from the National MS Society on the CCSVI studies did not supply any real hard data. It appears most of the teams are waiting for the 2 year mark to unveil their results.  This is disappointing, because the clock keeps ticking for those who have venous malformations and obstructions.

Dr. Fox's CCSVI study report caught my eye, since I've mentioned CCSVI and the effects of hydration many times on here, especially in relationship to hypovolemia, or low blood flow due to dehydration.

Here is the post where I mentioned the importance of hydration and blood flow.   Highly recommended reading:

http://ccsviinms.blogspot.com/2010/12/blood-flow-and-ccsvi-december-26-2010.html

I found it interesting that Dr. Fox's team is exploring hydration in relationship to CCSVI---and wondering if he will use hypovolemia as an explanation for CCSVI.

.....the state of hydration of the subject (whether they drank adequate amounts of fluids) could impact results of several of the criteria used to determine CCSVI. They concluded that these complications may help explain the mixed results reported thus far related to CCSVI and MS, and they have added to their aims a study designed to evaluate the impact of hydration on CCSVI assessments.

The reason this is important is that we know not everyone who has CCSVI is dehydrated.  My husband always drank adequate fluids, and he had two severely deformed jugular veins.  But adequate hydration IS essential for good bloodflow.

I also found another aspect of Dr. Fox's study interesting, in that Dr. Gabbiani has studied biopsies of internal jugular veins taken from living people with CCSVI, and found a collagen shift in the jugular vein tissue.  Wondering what Dr. Fox's team will find from autopsy tissue.  Looks like we'll find out in October 2011--which is sooner than the 2 year mark.

Dr. Fox’s team has also gathered autopsy specimens of venous tissue from 9 MS tissue donors and 6 donors who did not have MS. The team first had to develop and standardize techniques for studying these specimens for signs of CCSVI. They are analyzing their data and have submitted abstracts reporting preliminary findings related to this pathology study and their scanning results for consideration at the international ECTRIMS (European Committee for Treatment and Research in MS) meeting in October 2011. 

I'm going to be a glass half full gal today, and say that I am hopeful for these studies and all that we can learn to help pwMS and pwCCSVI.

Joan