Research is the world’s biggest industry. The source of all we believe starts with research. Conducting solid and rigorous clinical research is a formidable task. Once we feel that we have achieved our endpoints, there remains the considerable risk of exposing one’s work to the harsh light of criticism by publishing the results in a reputable journal, in our case a medical journal for review by one’s peers. Since our particular investigation was human study, we first must acknowledge that there are difficulties within any particular study on humans and there are no such studies that are without some flaws or errors. But the liability of conducting a study, no matter how formidable or daunting, and not conveying the data to the world by publishing it, is even a worse violation of ethical convention. In the broader world of experimental medicine, no medicine that is not a standard of practice should be performed without following the patients because not only is it unsafe to do so, but nothing is learned if we don’t. This includes medical tourism. Just imagine what we might have learned from the tens of thousands of MS patients who went to other countries around the world to procure the so called ‘liberation therapy’ — had they been followed in studies.
Research is what we at Regenetek started out to do when a protocol was advanced by our international team of physicians based on a hypothesis we contributed to in late 2010, early 2011. Unlike pure medical tourism, it was not offered until an IRB (ethics committee sanction) could be obtained through application and it was not promoted at any time due to ethics rules set by the Ethics Committee. Regenetek Canada was tasked with following the subjects who took the therapy. MS sufferers who learned about it and chose to take it were under no duress to select it. Informed Consent was required following extensive explanations including the concept of ‘patient-funded research’ (allowed within FDA exemption guidance: CFR – Code of Federal Regulations Title 21 Sec. 312.8). Patient/subjects understood there was a cost and chose to pay it. To accommodate the global population of patients, we spent a number of years developing a novel ‘patient-following’ cloud-based, personal device-accessed software that clinicians, investigators and patient/subjects within the study can use collaboratively from wherever they are in the world to monitor outcomes. Subsequently, we have offered to extend this virtual utility to other clinical studies and are now releasing versions of it for minimal cost to other trial sponsors (with this breakthrough technology, made HIPAA-compliant and data-secure, the first of its kind in the world, there is no longer a valid reason for clinical studies, or medical tour clinics anywhere to use the excuse that it is too expensive to follow patients or that such a service does not exist. It exists on an open platform for anyone to use).
The therapy itself was formulated on a proposition that seemed reasonable to the research team, and that the current research supported; that autologous (the patient’s own) stem cells directed toward the areas of vascular injury (the major veins) in the brain would heal the weakened endothelial tissue that caused the leakage of neurotoxic proteins (fibrinogen) through damaged venous tissue across the blood brain barrier. Inflammation due to an autoimmune response ensued along with the cascade of observed events (demyelination) leading to symptoms of MS. Jean-Martin Charcot (known as the ‘Father of Modern Neurology’) and Franz Schelling (a contemporary Austrian neurologist/researcher) among many others had determined that this initial venous vascular dysfunction in the brain is strongly associated with MS. There are many referential studies on this phenomenon that has been described for over 150 years so it’s not exactly a new discovery. But the research, heavily relying on that of Franz Schelling’s, pointed the team in a new direction and informed an authentic protocol. If effective it would stabilize endothelial function and could translate into delay or arrest of the conditions that cause MS and subsequent disability. That therapeutic protocol was registered for study in 2011 in India through the Independent Ethics Committee, Pune (IECP) and the actual procedures were carried out by world-class neurosurgeons, vascular surgeons and interventional radiologists from 2011 through 2014 in Pune, India.
There was much current research that informed the development of the protocol. For example, since 2010 Augusto Brazzini (a Peruvian Interventional Radiologist) had had great success with the super-selective placement of stem cells into the Circle of Willis in Parkinson’s patients. Stem cells that are infused in this area of the brain not only translocate, but effect adhesion, differentiate, effect paracrine signalling to mobilize other cells, and release cytokines (along with inhibiting fibrosis, apoptosis and inflammation), to potentially re-vascularize and replace dying cells in the dopamine-producing center of the mid-brain, the substantia nigra. He published a paper in the Journal of Vascular and Interventional Radiology (JVIR) on his research in 2010. In 2014 I had the great fortune to spend time with Brazzini in Lima, Peru where he does his research and we discussed the therapeutic imperative of ‘super-selectivity’. He shared with me that for the treatment of Parkinson’s, ‘the placement of a clinical dose of stem cells directly to or near the area of injury is at least as important as the type of cells that are used’. In his therapy, he was using a simple bone marrow extraction, and from that breakdown was infusing the entire population of cells from the sample directly into the posterior communicating arteries in the mid-brain that fed blood supply to the substantia nigra. If Brazzini’s treatment for Parkinson’s disease was as effective as it appeared to be in his research, was it possible to treat other neurodegenerative diseases the same way?
The international research team (including neurosurgeons, neuroscientists, microbiologists and interventional radiologists) had previously independently proposed that if enough stem cells could be similarly infused into the specific area of injury into the brain of an MS patient, this could potentially stabilize the vascular dysfunction that may cause MS in the first place. Schelling’s research on cadavers of MS patients in the early 80s, and his paper in 1986 on venous morphology and flow velocities, identified the specific vessels that must be treated. But if Brazzini’s protocol relied on directional arterial blood flow to supply the stem cells to the mid-brain, how would anyone conceiving of a similar protocol for MS, access the abnormal veins in the brain to infuse these cells when the flow is in the reverse direction? In my email discussions with Franz Schelling, he could provide no real insights into how this might be achieved. Therapy was not his objective. But any new research must consider the work of Paolo Zamboni, Schelling’s star student during that time. Zamboni, in his clinical study had revealed that the expansion of a balloon in the jugular vein, although not particularly effective in opening occluded cervical veins to re-establish normal flow in the long-term, was at least very safe. Surveillance protocols that include duplex sonography have identified that veins with occlusive lesions decrease flow and threaten patency (Compared to healthy controls, MS patients with restricted blood flow in cervical veins showed significantly lower net flows (p=0.027) which was associated with lower cerebral hemodynamic insufficiency scores in various studies by Zamboni, Zivadinov, Menegatti, at multiple centers). Although permanent reduction of occlusive lesions was not the goal, the hemodynamics of flow reversal now allowed access to the areas of injury (the cranial veins immediately distal to the cervical veins) with a clinical dose of the body’s own healing cells by allowing interventional radiologists to infuse the cells at the same time that the balloon was expanded. Since it wasn’t possible to safely manipulate the catheter to these cranial veins, the retrograde flow was what was required for the successful implantation of stem cells to these areas of morphologic vascular changes (pathology).
The outcomes of the therapy we investigated was known as the Combination Therapy Protocol or ‘CTP’ for short. It involves a combination of intravenous (internal jugular veins) and intrathecal (spinal space) infusions of autologous stem cells. The details of the protocol will be revealed with publication, but suffice to say that there have been compelling outcomes to date that have achieved statistical significance.
As we prepare to submit the first of the manuscripts for publication, I must acknowledge that this work has not been easy. For anyone who has followed our progress, that seems like an understatement. Indeed the study subjects themselves have been so tainted by the malice toward the research and the research organization by the sensationalist media in public news articles such that the data collected after the media stories appeared can no longer be used without introducing a considerable bias into the data. In any publication, the ‘post-media attack’ data could simply not be trusted, nor would it be viewed as reliable by our peers. That was the reality we were faced with in February after the errant attacks. But we had much good data that was gleaned before the bias was introduced so we endeavored to reconfigure it to narrower timelines post-therapy. Patient data gleaned from outcomes prior to January 2015 would not be considered to be distorted or in any other way, invalid. Although the measurements would be smaller, they would nonetheless be clinically relevant if they could be shown to be consistently and significantly changed as a result of the therapeutic intervention.
New Academic Interest
As a post-script to our study, even though the local media has unjustifiably characterized our research as ‘medical tourism masquerading as medical research’, the Regenerative Medicine Program at the University of Manitoba School of Medicine has been meeting in secret with some of the family members and the patients we are following, and are attempting to collaborate with several of our colleagues to evaluate and further the research that we started. Apparently they don’t perceive our science as flippantly or as malevolently as the local media. Their goal, should they proceed, is to combine therapeutic research with their bench studies. They have now contacted Dr. Augusto Brazzini who I spent time with in Peru in 2014 to discuss collaboration. Ostensibly they may plan to bring Dr. Brazzini to Canada to perform his Parkinson’s protocol under the auspices of the University of Manitoba and I believe that discussions are heading in this direction.
Nobody from the Regenerative Medicine Program has contacted me, even though without our input as well as the personal multi-million dollar investment in the research, would any of these meetings, or any future plans they might have to engage therapeutic research of this type, be possible. Without our considerable work in this field, they wouldn’t be exposed to the cutting edge of medical science or even be discussing eliminating a decade off their bench studies and proceeding to therapeutic research, and they certainly wouldn’t be speaking with Dr. Brazzini. My question is this: Since the protocol for MS we are studying was developed on the same principle of ‘super-selective’ placement of the cells as Brazzini’s Parkinson’s protocol, wouldn’t it be more appropriate to study Multiple Sclerosis in therapeutic studies in Manitoba — geographically, the area of the world with one of the highest incidences of MS (ie, Western Canada…340/100,000 pop)? It seems a shame to bypass MS when so many Canadians suffer with a growing incidence of this pernicious disease. A breakthrough therapy that follows our protocol and has a ‘made in Manitoba’ element would be both a political and scientific achievement.
Replication of the research must eventually be done and it should happen sooner than later. It could and should happen in Manitoba, given what’s at stake for a rapidly growing population of MS patients in this region (highest incidence of MS in the world). If asked, I would be happy to convene (in Winnipeg) my international colleagues who are the world-class Interventional Radiologists, Neurologists, Microbiologists and Clinicians engaged in the interventional research, to discuss our study, the considerable research that informed the development of the protocol, and the scientific principles behind the super-selective approach to therapeutic intervention that must be taken. I am prepared to reveal our procedural techniques in order to help the operators understand the complexity of the procedure. We have taped footage of the step-by-step endovascular procedures in the cathlab, which would be invaluable to such a study in the early stages, especially where the interventionalists are unfamiliar with the procedures. Finally, I am prepared to reveal our study data in advance of publication in a collaborative effort to aid in the expectations of the outcomes of this therapy at another center. To demonstrate both safety and efficacy, we will produce a dozen study subjects, all of whom have achieved a measured, statistically significant recovery outcome over more than 12 months post-therapy. It’s important that the consistently positive testimonies of these patients be heard by serious researchers and physicians in an attempt to understand the phenomenon since they weren’t afforded that opportunity by the media throughout their campaign to discredit, belittle and humiliate our organization and our research.
So with the patient outcomes we have observed and clinically measured, it is entirely possible that CTP therapy, possibly with minor variations, could be THE standard therapy prescribed for MS within the decade. What could be more elegant than treating an MS patient with their own stem cells in the same operating room within minutes of the harvest of these cells from their own posterior iliac crests (hip bones)?
Will it work for everyone? No specific treatment or combination of treatments works for every patient. The first goal after proving the therapy is safe would be to continue research on the etiology (causes) of the disease (MS) so that prevention would be as integral a part of the process as the treatment. Our first research manuscript, soon to be submitted for peer review with the goal of publication, will be the first such published research to provide evidence that the patient’s own cells can help to control, and improve function in a chronic, incurable neurodegenerative disease in a population of patients without producing more symptoms and without the enormous ongoing cost ($60-$150,000/yr each patient , and often greater costs as a result of being prescribed multiple medications), as well as the considerable side-effects of the meds. No medication has ever been shown to significantly reduce symptoms and produce increased function in patients over the long term. In most cases, MS progresses relentlessly despite these expensive meds (Shirani A, 2012).
If therapeutic research is their objective, the Regenerative Medicine Program will do well to critically study the Indian protocol and attempt to reproduce it. The department heads, researchers and clinicians within the University of Manitoba Regenerative Medicine Program have put enough credence in the science to meet with patient family members and colleagues of Regenetek in Winnipeg in early August and gave them ample time to tell their story and demonstrate their ‘truths’. They should be excited; the people in attendance were representing remarkable improvements in function and to their credit, have ignored the misrepresentations of Regenetek and our Indian clinicians’ research in the media. This meeting, during which time OUR protocol was produced by the researchers, I am told, is a matter of record in case anyone wishes to follow up. Certainly such a meeting is extraordinary and is an indication of an acute need to change the direction of research. I was further told from people inside the meeting that the Head of the Regenerative Medicine Program declared to the full body in attendance that they may wish to move the research to the therapeutic stage in Winnipeg, similar to what Regenetek and its Indian colleagues have already done internationally, and this is certainly good news….if it happens…
Faults in the Current Research Structure
Although I enthusiastically hope it happens, it would be a rare thing for even academic research into stem cell therapy to get off the ground at the U of M. Funding is the issue. Joseph Ross, a professor at Yale Medical School who has studied the issue of university-funded therapeutic research did a study in 2014. ‘Unfortunately the entire evidence base has been perverted. Corporate bias can be particularly strong. The odds of coming to a conclusion favorable to the industry are 3.6 times greater in research sponsored by industry than in research sponsored by government and non-profit groups.’ Peter Gotzsche, who wrote the book “Deadly Medicines and Organised Crime, How Big Pharma has Corrupted Healthcare“, says that the major drug companies are regularly engaged in fraud, bribery, and obstruction of justice. 95% of their research findings cannot be trusted and influencing the direction of research at academic institutions is a regular practice (Gotzsche P, 2012) .
Universities who do stem cell research (other than looking for drugs that are expressed by stem cells) must look for funding elsewhere and the corporate sponsors (Big Pharma) who refuse to fund it, often threaten to pull their entire grant budget if they don’t like what the university is investigating. Although the drug companies only sponsor about 20% of all academic research, they lever that contribution effectively and regularly threaten withdrawal of funding. Often they have drug company advocates at the top of the leadership at the universities who kill the research before it ever gets that far despite what direction the department heads and researchers want to go. This has been well-documented by the in-depth studies of Adriane Fugh-Berman in the last several years (on C-SPAN and worth the time it takes to watch it). And there has indeed been a devastating failure of stem cell-focused research programs when left to the open market for study and development for commercial use. Yes, this happens in Canada as well and we should not be so naïve as to think the backstories to the direction of research even at academic institutions aren’t studies in the influence of corporate authority and dominance over the medical industry. Until now, research programs for most diseases have been looking exclusively to pharmacological solutions, not cellular biologics. That is not to say that drug outcomes are always seen to be better than biological therapies for all diseases, but it’s much more difficult to patent a stem cell (especially an autologous cell) and it’s not an area that drug companies want to participate. Research into the efficacy of stem cell therapy is increasing, but there is far less of it compared to drug research and it certainly doesn’t have the backing of Big Pharma sponsorship.
In fact, it’s consistently been small innovative companies like Regenetek that have kept stem cell research and potential therapeutic solutions moving forward over the past few decades. But because of the small size of the companies and lack of funding for this research, the realization of the therapeutic potential of stem cell research has been slower than expected, and slower than the rhetoric of the media make the public believe. Despite this there have been some celebrated successes, in the case of Gordie Howe for instance.
With the complete failure of the major pharmaceutical companies to come up with anything other than disease modifying drugs (DMDs) for diseases such as MS, which fail to prevent decline or preserve functional activities in patients, other solutions must be researched and if successful, delivered. Based on the current DMD medications that are prescribed for MS, which can cost over $100,000 a year for decades for each patient, why should pharmaceutical companies change their approach? They are guided by the bottom line figures and research decisions are made in favor of the shareholders, not the patients they serve. The major pharmaceutical companies are not public benefactors. Says Navid Malik, a spokesperson for Big Pharma in a perfect summation: ‘A stem cell solution doesn’t fit well with an approach whereby it’s a chronic treatment and you take a pill forever.’ In fact up until now, Big Pharma has gone out of its way to place obstacles in the way of biological solutions and even the ability for companies like ours to carry out the research.
But if not us, who will do this research? Should we just wait for others to act? Well they haven’t done it, and if it could have happened it would have already. There are over 150,000 studies on cellular medicine registered and chronicled in the National Library of Medicine in Bethesda, MD., more than any other medical topic archived in the stacks. Yet we have only a few treatments with stem cells that have become a standard of practice in western medicine. Why is this? We already know that many types of stem cell therapies are highly effective but aren’t in practice at this time (and the physicians reading this know exactly what I’m talking about). While we wait unnecessarily, people are getting sicker and dying. Whatever Regenetek’s final fate, it’s important that we set the bar higher than those who have tried to scuttle our research and higher than those who are talented enough but aren’t brave enough to put their careers on the line for what they know to be right; to set the standard for exemplary behavior under fire and publish our data so that we might stir the imagination of those with the vision and the courage to take our findings to the next level and advance the art of the possible. However the research is designed, however it’s funded, if it’s done legally, ethically and with rigor, for the public good we must continue to attempt to provide evidence of efficacy.
The REAL Story
So could it be that the real story was missed entirely by the local media in not reporting some remarkable recoveries by the patient/subjects being followed by Regenetek? The press wrote their false prevarications while ignoring the appeals of patients themselves who were demanding their stories be told in print. Now, months later and too dug in to ever concede a whit of conscience or contrition, the local media have a lot invested in seeing both our research and the international research organization destroyed. Unless we go away completely with our tails between our legs, never to be heard from again, they don’t look so good. In fact, one or two celebrated and documented recoveries over time within the patient population, nullifies their denunciation of our research. It’s interesting to note that the Gordie Howe stem cell procedure was performed at a small foreign clinic using the same combination approach to the therapy (vascular as well as intrathecal), was done within a similarly designed study, charging exactly the same amount ($30,000) yet did not attract the frenzied media attack on the research that happened in Winnipeg.
Regarding this selective scrutiny, it hasn’t escaped our attention that some of the media aren’t just content to report the news. They have gone well out of their way to insert themselves into making the news; for example, stating in print over and over again that there are police and revenue agency investigations happening for reasons of fraud when there are none and never were, presumably to divert attention from the efficacy of the research. In fact, the fraud committed was committed against Regenetek (and Genesis Institute by extension), and the matter remains under a growing international investigation at this time (and that is another fascinating aspect of this story that speaks to motivation — and a topic for another day as more agencies are taking a keen interest in the motivations of the disruptors — stay tuned).
In any clinical study, even one or two subjects out of many who over time demonstrate functional improvements of statistical significance that cannot be achieved with the existing treatments, is certain justification for continuing to investigate a novel therapy. In the case of the Regenetek/Genesis study, it is undeniable that there are scores of subjects who have significantly improved and have maintained their improvements over months and years. And that is what our publications will provide evidence of. Likewise, the reason there is sudden intense interest in this protocol from the university’s regenerative medicine program, is because of the dramatic demonstration of significant health improvements with the absence of symptoms. So there is cognitive dissonance in that we haven’t gone away, continue to explain the science, and will passionately plead our case for the continuation of this research until we are heard. We will exist long enough to publish our data, which is what we set out to do in the first place. And although we are no longer involved in collecting data, we recognize that only a single research facility in the world is currently performing these same therapies with the same consistently positive results. For many of the study subjects, this therapy has withstood the test of time, and given those significantly positive outcomes still being followed in an NIH-registered study, there will undoubtedly be more, and as a result, growing interest from academia in this novel interventional approach.
And that was the entire point. The Regenetek research program only existed to produce evidence of a new scientific advancement that would help the many thousands of people world-wide who live with MS, and the many more thousands who will develop the disease with increasing frequency at some point in their lives. If that isn’t already clear, it will become clearer as time goes on and the data we collected becomes a matter of public record.
It also exists for others, like the Regenerative Medicine Program, to attempt to replicate and clinically measure the outcomes which, I am confident in saying, can be safely and effectively achieved, provided that the therapies are conducted appropriately and with rigor by competent operators. On the other hand, the newsmedia exists for one purpose, and that is a commercial purpose. ‘News’ is biased by nature. Newspapers don’t sell without embellished and salacious articles and readers need to be mindful of that when trying to separate the fact from their fictions (their so-called ‘story angle’) designed to sell newspapers. The media; who were so invested in the salacious story they had already pre-written that they didn’t even bother to interview second sources, do the appropriate fact-checking, listen to what most of the patients were telling them, or sit down with us to discuss what our objectives were with the credible research we were doing. Many of the patients I have spoken with since were disgusted by the way media interviewers ran roughshod over them — from the leading questions that marginalized their responses, to the fact that their personal stories of recovery/return to health, readily offered — were never told in the heavily biased articles. Apparently MS patients returning to long-term health, absent of symptoms, and regaining function that they haven’t had in years isn’t newsworthy enough for the local media.
So starting fresh with new academic interest in CTP and potentially a new research organization willing to investigate, providing they can get the funding, we now may have another important opportunity to study this novel and fascinating approach to therapy for an incurable neurodegenerative disease. There is urgency to move to therapeutic research from bench trials. With the rate of Relapsing-Remitting MS (RRMS) increasing at alarming rate (globally, not just northern latitudes), especially in females, by the estimate of the World Medical Association and many new studies, we cannot wait a decade for yet another generation of marginal drugs to fail. Multiple recent epidemiological studies corroborate an increase of the female to male ratio among RRMS patients over the past 60 years and a world-wide increase in MS overall, that has seen a shocking 50% rise in MS in the last 25 years (Neurology, vol 32, p 1207).
I wonder how the reporters will file their stories when they are compelled to report that the protocol that was first studied by Regenetek, the very one that they have attempted to discredit, IS the protocol that is attracting new attention from academic researchers, and potentially the therapy by which all MS patients will be safely and effectively treated at some date in the near-future? No amount of hyperbole and spin will stop the true nature of the disease (MS) from being recognized, and a potentially effective, long-term treatment from eventually being practiced through good, solid and ethical research. We need to ask ourselves, if the media continues to neglect their journalistic integrity and create obstacles for this research, whose side are they on and what are their motivations in doing so?