The discovery of a cure for MS will not be attributable to a single medical breakthrough but a series of medical discoveries and innovations leading to the cure. This process will involve biochemists and vascular researchers; physicists and radiologists; engineers and neurosurgeons, immunologists and geneticists among many other scientific disciplines. Furthermore, evidence being produced in current trials and studies will establish that some types of neurodegenerative diseases will not be the exclusive area of a single medical specialty, but will require multidisciplinary teams to work collaboratively. Eventually (but not through the current government-sponsored Clinical Trials), the new hypothesis of a vascular disease connection with MS will be validated. But a different approach will be required; the theory that a simple dilation of the jugular veins can achieve a cure for MS oversimplifies the explanation of the disease pathways and ultimately obscures therapeutic objectives. Since it was proposed three years ago, it has also politicized a specific disease like never before and has polarized stakeholder interests on two sides of an argument. Biases abound within every stakeholder group since this truly is a ‘life and death’ struggle to either prove or reject any vascular connection to the disease.

Anyone looking at the empirical evidence demonstrated by the growing number of MS patients who are commonly affected once the retrograde blood flow pressure on the brain is relieved by expanding the occluded jugular veins should agree that Zamboni’s hypothesis is more or less correct; that an equalization of the outflow of blood from the CNS to the heart muscle is essential to reducing the presenting symptoms of MS (this was even admitted by Dr. Pryse-Phillips of the NL Study). But the surgical procedure of neck vein dilation by itself will not come close to providing the eventual cure. Once the vascular pressures are balanced, only a correlation between vascular pathology and the disease itself has been demonstrated. The occluded neck veins do not explain the autoimmune trigger that causes the disease.

Connecting those dots via the clinical findings from the effect of autologous cells transplanted to the MS brain goes a long way toward the explanation, but again does not identify the trigger. In individuals predisposed to MS, whatever prompts the autoimmune response, inevitable and irreparable damage to the myelin and the interlaced axonal matrix occurs through the pattern of the disease. In multiple clinical trials, suppression of the disease event cascade has been demonstrated with the introduction of Mesenchymal stromal cells (MSCs) to the diseased CNS. Once these cells are introduced, the resultant biochemical event sequence has been observed, biochemically identified, measured and described in several important trials. Where the retrograde pressures caused by the stenotic vessels reflux and deposit deoxygenated and iron-rich hemoglobin on the myelin covering of the CNS, MSCs respond by inducing suppression of various immune cell populations and inhibit white blood cells from evaluating the sites of insult and erythrocyte extravasations. But it’s still not known why only some people get MS since the same diseased pathology and internal biochemical conditions exist in human populations that never exhibit the autoimmune response.

The good news is that it may not have to be known for the time being. The therapeutic benefits of MSC transplantation have been clinically observed in human subjects. The stem cells, once introduced to the CNS, create the same internal environment where the MS patient’s over-aggressive immune system is suppressed. These stem cells, if present in sufficient numbers, then locate themselves to the areas of disease to replace the damaged nerve and tissue cells. In therapeutic trials on human subjects, the recovery of neurologic deficits in many patients has been remarkably rapid and complete.

For MS patients transplanted with stem cells that suppress the disease syndrome and go on to regenerate all tissue and neurons that have been damaged by the disease, the obvious question is then whether the diseased neck veins need to be treated at all? The answer may lie in the MS patient’s abnormal vein pathology. By establishing a diagnosis of Chronic Cerebrospinal Venal Insufficiency, a disease condition has been noted. Furthermore a clear correlation has been established between the pathology and the disease through statistical and observational evaluation. In some southern countries where MS does not exist in numbers in the general population, CCSVI in the jugular veins has been noted and corrected as treatment for some types of optic neuritis, a symptomatic indicator for MS (and another autoimmune disorder). Once the neck veins are widened, the symptoms of optic neuritis are alleviated. Minimally invasive procedures to treat optic neuritis (and other specific conditions) by way of jugular venoplasty have been going on in some countries for the decade before Zamboni publicized his liberation theory to the world in 2009. To several groups of neurosurgeons in India, and South America, Zamboni’s theory was no surprise; in fact it made perfect sense. This therapeutic treatment modality for an autoimmune disorder that is not considered to be MS (possibly Benign MS), yet has some of the same presenting symptoms of MS, is further confirmation of a vascular connection to the disease. Therefore the pathology of the neck veins in MS patients cannot be ignored. And if this statement is accepted as true, then there are many more questions that fall into line.

The greater problem is what to make of the vein dilation therapy as it’s currently being practiced on MS patients by Interventional Radiologists (IRs) in clinics around the world? While MS patients in the thousands fly hither and yon to receive the ‘liberation therapy’ on an outpatient basis claiming it is their right to seek alternative treatments, are they really receiving the most effective therapy for their disease? Or is the ‘liberation therapy’ only one part of the ‘bandwidth’ being treated in a general disease condition that requires a ‘spectrum’ approach to treatment?

To start with, the high rate of thrombosis and restenosis that occurs immediately post-venoplasty procedure indicates that it should never be considered as an outpatient procedure; the immediate risks are too high. Yet up until now the clear need to monitor patients post-procedure to avoid risk of complications has not been a focus of either therapeutic practice or of the research, and at least therapeutically, has not been seen as necessary by the practitioners. This avoidance of post-procedural aftercare and lack of follow-up with MS patients just having undergone venoplasty is remarkably at odds with the evidence and consistent with the financial biases inherent in the current system of management of CCSVI. The Interventional Radiologists who are practicing the ‘liberation therapy’ as the business of medical tourism are the same practitioners who wrote the protocols for the current NIH-approved trial in Albany and have neither defined aftercare beyond follow-up imaging, nor included provisions for potential adverse events, post-procedure.

Trouble Ahead for Proving the Vascular Hypothesis

And what happens when an aftercare protocol that supports post-procedure wound healing in the newly remodeled but weak jugular veins is ignored by the IRs writing the current Trial Protocols? If the NL Study method is replicated in the larger New York Trial currently partially funded by the Saskatchewan government, the patient outcomes will, quite predictably, be precisely the same (within statistical margins for error). The conclusion of ANY trial that ignores the clear need to pursue a written aftercare protocol is doomed to repeat the NL Study findings.

The obvious immediate effect will be that unless this evidence is taken into account and the protocols are strengthened for these new trials, the ‘liberation therapy’ (as it is currently being practised) will not be approved. No medical licensing board will sponsor a procedure for an outcome where the average subject’s vein restenoses after 3 months. And in the face of the rejection of a hopeful therapy that was seen to be at least partially effective, the MS community, citing that it is their right to seek alternative therapies where the current ones are ineffective, will dig their heels in on one side, and the medical establishment citing lack of long-term efficacy on the other will continue to refute the Zamboni hypothesis in its entirety.

Even though there is good evidence to support a number of potentially effective therapies and sequences of therapies in combination for the treatment of MS that includes both vein dilation and stem cell implantation into the dilated veins, the complexity of the science of MS seems doomed to be overshadowed by the politics of MS. With what has been ‘proven’ in trials outside of the ones that are only intent on investigating a simple connection to a vascular cause, new strategies could be developed by the stakeholders in a spirit of cooperation. However, with the pharmaceutical industry now banking on a next generation of drugs that involve expensive ‘non-injectible’ immunomodulators (DMTs) for Relapsing/Remitting forms of MS, it’s highly doubtful that there will be ‘peace in the house’ anytime soon. As anyone with MS knows, drug treatment by itself does not help guide us toward a cure for MS either, but Big Pharma will not give up what has been their exclusive turf without a fight. The prospect of licensing these new medications for MS has been a major objective of at least 3 of the biggest pharmaceutical companies for years.

Some background on this will put MS into context as to where the disease is on Big Pharma’s radar. The conventional and long-established approach by Big Pharma was to invest heavily in a few promising molecules, convert them into blockbuster drugs, then promote, protect and prolong their patents. The strategy worked well for many years. But in the face of burgeoning world populations that demanded REAL and cost-effective cures (not usurious long-term medication regimes), the global marketplace has transformed significantly. The Life Sciences Industry has supplanted Pharmacy. Consequently, even though Big Pharma lost its exclusive global control over the medical solutions industry, in countries where these 20 companies still have heavy political and financial influence over governments and medical systems (US, Canada and Europe), their stated strategy has been to fund the disruption of any presentation of proof of efficacy for alternative life science-based therapies and methods that do not include pharmacology (and they have been completely supported by the FDA in this). So expect them to spend many millions more to keep MS under their exclusive control as it’s one of the few bright stars left in their decaying galaxy.

Although MS patients who pushed hard for the clinical trial investigation into CCSVI are now hopeful they are finally occurring and that they will at last prove efficacy for Zamboni’s hypothesis, they are unwittingly supporting a trial protocol that the pharmaceutical companies know will fail. With such high rates of restenosis already among those who have been treated, and in many cases retreated again, it’s perhaps the ultimate irony that MS patients have been paying so much to actually disprove the vascular correlation to MS…for the time being. Stay tuned.