Wednesday, February 21, 2018

Tisch Center MS Stem Cell Trial: Interview with Dr. Saud Sadiq, Director and Lead Research Scientist (Part Two)

Dr. Sadiq and research staff at the Tisch Center
The Tisch MS Research Center of New York (click here) will soon begin its first-ever FDA approved Phase 2 regenerative stem cell study for multiple sclerosis. Last week, I published the first part of my interview with Dr. Saud Sadiq, the Director and Lead Research Scientist of The Center, which discussed  the Phase 1 study and its results (click here). As promised, here is the second part of our discussion, which focuses on the upcoming Phase 2 study, the Tisch Center's new stem cell laboratories, how stem cells might help repair damaged nervous system tissues, and some of the other multiple sclerosis research projects being conducted by Tisch Center researchers and scientists.
This interview has been lightly edited for readability, and I’ve added some “WK Notes,” which attempt to translate overly complicated medical jargon into plain English.

WK: The Tisch center is now preparing to embark on Phase 2 of your MS stem cell trial. When do you expect this next phase of the study to get started?

Dr. Sadiq: After the  Phase 1 study ended, we made a commitment at The Tisch Center that we needed to make our stem cell laboratories absolutely state-of-the-art. We’ve invested heavily in building a new stem cell lab, which is being completed now. Everything’s automated, it’s a next generation stem cell facility that will be functional and certified in about a month and a half. Then we will be prepared to start the Phase 2 study. We do still need some additional funding for Phase 2. We are applying to the National Multiple Sclerosis Society for a grant. Though they didn’t support Phase 1, given the impressive results of that trial we are hopeful that they will support us as we go forward. We also expect private contributions to help fund Phase 2, as these have always been the lifeblood of the foundation.

WK: How many patients will be involved in the Phase 2 study?

Dr. Sadiq: There will be 50 patients involved. It will be a double-blinded crossover study specifically designed to establish the effectiveness of the neural progenitor stem cells we've developed in our laboratories. So it has an entirely different aim than the Phase 1 sstudy, which was intended primarily to determine the safety and tolerability of our stem cell procedures. We are going to give Phase 2 study participants six treatments, one every two months. Therefore there will be more treatments given in greater frequency than in the Phase 1 study.

WK: So, with 50 patients, 25 will be getting actual stem cells, and 25 will be getting placebo treatments?

Dr. Sadiq: Yes, in the first year 25 subjects will get treatment and 25 will get placebo, and in the second year the ones who got placebo will get treatment and vice versa.

WK: What will the patient population look like for this Phase 2 trial?

Dr. Sadiq: The patients for this trial will have to meet much tighter inclusion criteria then the patients in Phase 1. They all must be diagnosed with SPMS or PPMS. They have to be ambulatory, so they’ll all have EDSS scores between 3 and 6.5. The FDA is requiring that we have an equal distribution of the EDSS scores. So there will be equal numbers of patients distributed between all the points along the EDSS scale. The other limitation is that all patients will need to have had the disease for 15 years or less.

WK: Will the study participants continue with their disease modifying drugs?

Dr. Sadiq: Yes, but they can’t have switched medications within six months from the start of the trial.

WK: Once they are in the trial they’ll have to remain on the same DMD for the duration of the study?

Dr. Sadiq: Yes.

WK: What will be the total duration of this trial?

Dr. Sadiq: There will be two years of study and placebo, and one year of follow-up. So a total of three years.

WK: Just to be clear, in the third year none of the patients will be receiving stem cells?

Dr. Sadiq: That’s correct, in the third year there will be no stem cells and no placebos. After the second year, all patients will have received six treatments. The patients who received stem cells in the first year will have placebo in the second year, and the patients who received placebo in the first year will receive stem cells in the second. The third year will be for observation of all patients.

WK: For all the folks out there with RRMS, if the Phase 2 trial proves successful then the stem cell protocol developed at Tisch could be applied to them as well, correct?

Dr. Sadiq: For patients with relapsing-remitting disease who experience a relapse that results in damage from which they don’t recover, stem cells could be introduced in an attempt to repair that damage. That would be the dream scenario, and it could render disability resulting from MS a thing of the past. But at this point were getting ahead of ourselves…

WK: As we move forward into a world in which stem cell treatments for MS become a standard of care, would you anticipate that patients will need continued and repeated stem cell treatments to maintain or advance whatever benefits they realize until a cure is finally found for multiple sclerosis?

Dr. Sadiq: Yes, that’s likely. I think the Phase 2 trial will really go a long way towards answering that question. It will be important to ascertain what happens to patients in the years after they receive their stem cells. Do they maintain their benefits, do they return to baseline, or do they fall somewhere in the middle? These will be significant findings. The design of this crossover trial will allow us to figure that out. My feeling going in is that patients will need stem cell treatments over the long-term, maybe not six a year after the initial treatment., but perhaps less frequently to maintain whatever improvement is seen.

WK: The neural progenitor cells developed by the Tisch Center – or any regenerative stem cells, for that matter – don’t directly address the disease process, correct? If so, does the disease remain active despite the use of these stem cells?

Dr. Sadiq: Yes, that’s right, the cells are not a cure for the disease. They hopefully secrete trophic factors that would stimulate the body’s own progenitor cells to activate and induce repair at sites of injury. (WK Note: trophic factors are elements which cause the body to maintain or start some action, in this case repairing damaged nerve cells and possibly affording some protection against attack from immune cells.)

WK: So, the stem cells may not necessarily repair injury all by themselves, but they may jumpstart natural repair mechanisms within the bodies of the patients in which they are implanted?

Dr. Sadiq: I think that’s the most likely mechanism. Whether they play some direct role is something we have to figure out, but I think it’s more likely that they’ll turn on a patient’s own progenitors and also create a trophic environment that acts as a shield from the immune system and allows the body to make repairs.

WK: I know that stem cells aren't the only focus of the Tisch Center's researchers and scientists. I’d like to touch on The Tisch Multiple Sclerosis Research Center of New York itself, and some of the other areas of research that are currently ongoing in The Center’s labs. Could you give us a peek inside and tell us about some of the other projects Tisch researchers are working on?

Dr. Sadiq: Well, at the Tisch Center our original goal was to identify the root cause of the disease. It may be some type of immune cell, or some unidentified infectious agent, or maybe some other environmental element. Once we can identify the cause of multiple sclerosis, we can then methodically work towards a cure. And finding a cure is our ultimate goal.

WK: So, the Tisch Center currently has researchers who spend their days searching for the root cause of multiple sclerosis?

Dr. Sadiq: Yes, absolutely. I try to focus on the real challenges that I see as a clinician treating patients every day. My focus is on trying to understand primary progressive MS, which is perhaps the most challenging form of MS as far as treatment is concerned. There are very few treatments that can alter the course of progressive MS. We’ve created an animal model in our lab to try to understand the mechanisms of progression and why remyelination does not take place at all in this form of the disease. In relapsing-remitting MS we see damage occur and then some repairs get made by the body, especially in early disease. This is something not seen in progressive MS. We need to understand the mechanisms of progression better. We are also focused on cognition dysfunction because that can really dehumanize the patients who suffer from severe cognitive deficits.

We are also hard at work identifying biomarkers that can indicate the activity and severity of the disease. We’ve published a lot of papers in this area. We are doing a lot of work on metabolic dysfunction in the central nervous system in MS, and hopefully, that will lead us to readily identify markers that can pinpoint progression and disease activity, which will, in turn, allow us to assess the effectiveness of treatments in individual patients. In conjunction to the Phase 2 stem cell study itself, one of our aims is to analyze the spinal fluid of all of the study participants for markers that may predict which patients are going to get better by Identifying which patients experience actual repair and remyelination. The goal of identifying biomarkers is to be able to tailor treatments to each individual patient, specific to them and the intricacies of their disease. MS is a very heterogeneous illness, meaning that it affects each patient differently. Through the use of biomarkers, we hope to be able to address these differences on a patient by patient basis.

WK: The Tisch Center is not affiliated with any hospital or academic institution, correct, so it’s an entirely independent research entity?

Dr. Sadiq: Yes we are completely independent. We run Tisch like an academic center in every regard. We have guest speakers and all of the activities that would be associated with typical University research centers, but we are not affiliated with any academic centers. We retain absolute independence in choosing our areas of research.

WK: If you don’t have any of these affiliations, how is all of the research we’ve discussed funded?

Dr. Sadiq: We rely entirely on grants and donations. We use almost all the funds raised directly for research. Fully 90% of all monies raised goes directly into research, which is really an extraordinarily high number compared to other organizations. We keep expenses very low, so only a small percentage of funds raised go towards administrative costs and other such overhead. All of our tax forms and documentation in this regard are available online.

WK: My understanding is that you are not currently receiving any funding at all from the National Multiple Sclerosis Society. Is this correct?

Dr. Sadiq: Yes, that's right, we’ve had some bad luck with the MS Society, but they promised to look into our Phase 2 study, and I’m putting in a grant application. Hopefully, this time they’ll get involved.

WK: Obviously, the Tisch family (click here) is involved, but where does the rest of the Center’s funding generally come from?

Dr. Sadiq: The Tisch family is a very big supporter, but so are our patients and their loved ones. We have a very loyal following of patients and their families and other supporters that really enable this to happen. They’ve been supporting us for close to two decades, even before we were formed as an independent center.

WK: How much is this Phase 2 trial going to cost?

Dr. Sadiq: The build-out of the laboratory cost $5 million, and that’s a done deal. The trial itself calls for another $4 million, and we are currently raising funds for the study itself.

WK: So funding is still needed for the Phase 2 trial?

Dr. Sadiq: Yes.

WK: Well, speaking strictly for myself as a patient who has been ravaged by this disease, I can’t think of any cause more important and worthy of donations.

Dr. Sadiq: That’s very kind. Maybe I should hire you as a fundraiser…

WK: You can pay me in stem cells… Even though I know I don’t qualify for the trial because of my  level of disability…

Dr. Sadiq: That’s true, but don’t ever lose hope. Every day researchers here at Tisch and others around the world are working hard towards solving the puzzle of MS. I’m personally obsessed with curing multiple sclerosis.

As a patient of Dr. Sadiq’s, I can attest to his obsession with curing the disease. The man works at least six out of every seven days and even has a bedroom behind his office at the clinic affiliated with the Tisch Center. The clinic is called The International Multiple Sclerosis Management Practice (click here).  I’m also acquainted with some of the researchers at the Tisch Center, who are so dedicated that they'll even put up with my incessant questions when I manage to corner one of them with my wheelchair.

For those interested in donating to the Tisch Center, you can learn about the various ways to contribute by (clicking here). If you’d like to encourage the National Multiple Sclerosis Society to get behind the first ever FDA approved Phase 2 MS stem cell trial with a nice big grant, here’s a webpage with contact info for all of the Society’s senior leadership (click here). Please be polite If you do reach out to the NMSS. As my grandmother always told me, you can catch more flies with honey than you can with vinegar…

Wednesday, February 14, 2018

Tisch Center MS Stem Cell Study: Interview with Dr. Saud Sadiq, Director and Lead Research Scientist (Part One)

The Tisch Multiple Sclerosis Research Center of New York (click here) recently published the Phase 1 results of the first-ever FDA approved multiple sclerosis regenerative stem cell study (click here). The results created quite a buzz in the MS community, as the headline results stated that 70% of trial participants experienced increased muscle strength, and 50% saw improved bladder function. As the study included only patients with progressive MS, many of them with advanced disability, these results seem especially impressive.

Given the level of interest in this trial and stem cells in general, I thought it important to interview the man behind the study, Dr. Saud Sadiq, the Director and Lead Research Scientist of the Tisch MS Research Center. Luckily, Dr. Sadiq has been my MS neuro for the last 14 years, so a simple phone call was all that was needed to set things up. Dr. Sadiq and his researchers had been working towards this Phase 1 study for over a decade. Since the Tisch Center is not affiliated with any academic or healthcare institution, all monies for the trial were raised privately through a certified nonprofit foundation.

My interview with Dr. Sadiq is quite long but full of important information, so I’ll publish it in two parts. This installment will explore the recently released Phase 1 trial results and their potential implications. The next installment will include an overview of the upcoming FDA approved Phase 2 trial, as well as a discussion of how regenerative stem cells might work and their possible impact on the treatment landscape of multiple sclerosis. It also covers some of the many different areas of groundbreaking research currently underway at the Tisch Center's laboratories. I’ll publish the second installment next week.

This interview was lightly edited for readability. I’ve included some “WK Notes”, which explain in layman’s terms some of the more complicated medical jargon used in the discussion.

WK: Dr. Sadiq, you recently published the results of your Phase I MS stem cell trial, and they look quite strong. To start, can you tell me about the patient population of the study?

Dr. Sadiq: The patient population consisted of patients with clinically definite multiple sclerosis who had either secondary progressive or primary progressive MS. They had relatively stable disability scores – we use the EDSS scale to assess disability scores – in the years preceding inclusion into the study. Their EDSS needed to have not changed in the six months proceeded the study. Of the 20 people in the study, 10 of the patients we included used wheelchairs or had EDSS of 7.0 or above, and another 10 patients had an EDSS of between 3.5 and 6.5. The majority of patients were in the more disabled category and were using aids such as canes or wheelchairs.

WK: Why didn’t the study include any relapsing-remitting patients?

Dr. Sadiq: Well, remember, this was a Phase 1 trial that was designed primarily to assess safety. Relapsing-remitting patients tend to do well with disease modifying treatments, so evaluating recovery would have been much more difficult, even though this wasn’t a primary focus of this trial.

WK: You mentioned disease modifying drugs. Were the patients chosen for the study on disease modifying drugs, and if so, did they continue them throughout the study?

Dr. Sadiq: Yes, most of the trial subjects were on the drugs we commonly use to treat MS, including Tysabri, Rituxan, and intrathecal methotrexate (WK note: intrathecal (spinal) injections of methotrexate is one of Dr. Sadiq’s preferred treatments for patients with progressive MS. He also treats many of his progressive MS patients with Rituxan).

WK: What was the age range of the patients?

Dr. Sadiq: The youngest patient was in his 20s, and the oldest were in their 60s.

WK: Let’s talk about the type of cells that were used. These were not raw mesenchymal stem cells, which are the most common type of cells used in other stem cell trials and in for-profit clinics, correct?

Dr. Sadiq: That’s right. Basically, in our laboratory, we take a patient’s bone marrow and separate out the mesenchymal stem cells. We then purify and clone them, and then freeze them for use in subsequent treatments. The cells harvested from one bone marrow extraction – we harvest from the breastbone – can be used for multiple procedures. Before the actual treatment, the cells are then grown to about 100 million mesenchymal stem cells which we then convert into neural progenitor cells, cells which are committed to a neural lineage (WK note: neural progenitor cells are stem cells specific to the central nervous system). We usually get between 5 million and 10 million neural progenitors, and that’s what we inject into the spinal fluid of the patients.

WK: What exactly are neural progenitor cells as compared to raw mesenchymal stem cells?

Dr. Sadiq: Mesenchymal stem cells have the ability to differentiate into several different types of tissues. They can turn into fat cells or cartilage cells, but they can also differentiate into heart cells and liver cells, among others. Because we were injecting cells directly into the spinal fluid, we wanted to commit them to neural lineage so they would not differentiate into other kinds of tissues once inside the patient.

WK: I understand that the transformation process that turns mesenchymal stem cells into neural progenitors is something that was developed exclusively in the Tisch Center’s laboratories?

Dr. Sadiq: Yes, we published the process in a number of papers. The details of the differentiation process were detailed in these reports.

WK: So, the details of this process aren’t a secret, they can be replicated in any stem cell laboratory?

Dr. Sadiq: Yes, between this paper and previously published papers all of the details are available.

WK: To your knowledge, though, the Tisch laboratories are the only ones using this process?

Dr. Sadiq: Yes.

WK: Let’s talk about the treatment protocol that was used in this Phase 1 trial. How many stem cell treatments did the trial subjects get, and at what time intervals?

Dr. Sadiq: In this Phase 1 trial, we used three treatments on each patient, and the treatments were given every three months. We used between five and 10 million cells for each treatment. So, in this trial of 20 patients, we did a total of 60 stem cell treatments, and roughly 80% of those involved the injection of 10 million neural progenitor cells.

WK: How long did the study last? And was there a placebo control group?

Dr. Sadiq: The trial lasted two years, and there was no placebo control group. The capacity of our laboratories at the time was a limiting factor, so we had to stagger the treatment of patients.

WK: Even though the trial lasted two years, none of the patients received more than three treatments, and they all received them at three-month intervals, correct?

Dr. Sadiq: That’s right, nobody got more than three treatments.

WK: Okay, let’s move on to the topic that’s probably of most interest to patients, the actual results that you saw from the trial. The headlines were that 70% of the patients are an increase in muscle strength and that 50% saw improvement in bladder function. Could you give us some details on those numbers?

Dr. Sadiq: I think the main thing that has to be stressed is that the study was designed to look at safety and tolerability because nobody in a trial setting had previously injected stem cells multiple times at regular intervals into patients. We really had to establish safety and tolerability. We did this successfully, as all patients received all of their treatments and tolerated them well. There were no adverse effects except for very mild headaches and fever, which were transient and generally didn’t last more than 24 hours. There were no hospitalizations and no deaths, and this safety profile was really the primary purpose of this Phase 1 study.

As to the question of efficacy, we have to be very careful because this was not a placebo-controlled or blinded study, and most of the patients expected that they would get better. What we did see when assessed by muscle exam using the standard assessment tools – which were performed by a neurologist who wasn’t involved in the administration of the cells – was that 70% of the treated patients did see an increase in muscle strength in at least one muscle group. In addition, 50% of patients had significant bladder function improvement.

WK: Did some patient groups appear to respond better than others?

Dr. Sadiq: Yes, although patients did tend to improve across the board. Not unexpectedly, the less disabled they were, the more likely they were to improve. Overall, the less disabled did better than those with higher degrees of disability. Also, the secondary progressive patients tended to do better than the primary progressive patients. But remember, these were very small numbers, only a total of 20 patients of which only four had PPMS. But generally, we saw a drop off in response rates in patients with EDSS 6.5 and above.

WK: Why do you think there was this drop-off in efficacy seen in patients with EDSS 6.5 and above?

Dr. Sadiq: I think the integrity of axons is probably a key factor in whether they will rehabilitate or not. If you still have an electrical connection, it’s easier to repair, and scar formation from lesions probably also impedes repair. The less structural damage there is, the easier it is to repair the problem.

WK: What are your thoughts on repairing the damage of patients with higher levels of disability, who currently must rely on wheelchairs?

Dr. Sadiq: I think these are our hardest challenges. Once we can figure out how to eliminate scar tissue in the central nervous system, that will really open the door (WK note: scar tissue is created by the damage done by long-standing MS lesions). At one point we were using enzymes to try to eliminate scars. Once we can understand not just remyelination but also the regeneration of axons, I think that will be the way to achieve the goal of restoring function in more disabled patients (WK Note: axons are the long threadlike part of a nerve cell along which impulses are conducted from the cell body to other cells). That’s why we are so focused in our lab in trying to figure out primary progressive multiple sclerosis.

WK: Were any of the patients complete nonresponders?

Dr. Sadiq: Yes, there were. Some of the PPMS patients as well as some of the more disabled SPMS patients.

WK: You mentioned the lack of a placebo-controlled group. I’d like for a minute to discuss the placebo effect because many patients don’t, I think, have a very good understanding of what the placebo effect actually entails. Many believe that when improvements are attributed to the placebo effect that these benefits are being disparaged as imaginary or “made up” by the patient. Could you comment on the science behind the placebo effect?

Dr. Sadiq: The placebo effect is real. It’s scientifically shown to be real. Even in cancer trials, whatever the mechanism, it’s real. It’s not simply psychological. It’s a conviction where the patient thinks they are going to get better and somehow that has a physical impact. Now whether the brain produces certain well-being cytokines or humoral factors or if you get an endocrine surge, somehow that has a positive effect that we still don’t fully understand. Since the late 1950s, the placebo effect has been recognized as a genuine phenomenon. In fact, there is a case of a cancer patient who got cured even though they had been given a placebo and not the drug being tested. So it’s not just some insignificant, mild effect. Generally, it’s considered that in any study without a placebo arm there’s about a 30% effect that can be attributed to placebo. This is real, when the patient is hopeful, the patient often feels better.

The thing about our study which is encouraging and leads me to believe the improvements we saw are not all attributable to the placebo effect is that we saw the most improvements in the patients that were the least disabled. This is something you would expect to see in a double-blind trial. In our trial, we probably chose the worst patients to study in that they had the disease for many years and most of the patients had significant disability. Our mean EDSS was 6.8 at baseline. Our average disease duration was about 18 years. These are never the patients who are chosen for pharmaceutical company studies, who are generally much less disabled and have shorter disease duration. The patients we used actually stacked the study’s chances against getting any positive effect.

WK: Just to be clear about EDSS, what’s the difference between 6.0, 6.5, and 7.0?

Dr. Sadiq: 6.0 is somebody who needs a cane to walk, 6.5 is somebody who needs bilateral assistance like a walker or bilateral crutches, and a 7.0 is a somebody who requires a wheelchair.

WK: In the trial, what kind of results did you see in patients who were EDSS 7 or above?

Dr. Sadiq: We saw two patients who had not been able to take more than a step or two who after treatment were able to walk with a walker for 25 feet. Whether that was placebo or not, I don’t know because this level of effect hard to explain. This was out of 10 patients who needed wheelchairs. It’s certainly intriguing.

WK: So two out of ten patients who hadn’t been able to ambulate at all and were entirely reliant on wheelchairs before the trial were able to walk with the aid of a walker for 25 feet after the study, correct?

Dr. Sadiq: Yes.

WK: Well, placebo or not, that seems like a remarkable result.

Dr. Sadiq: Yes, but we need to see if similar results are seen when we do the Phase 2 trial, which will be specifically designed to assess efficacy.

I hope readers have found Part One of my interview with Dr. Sadiq useful and informative. Look for Part Two next week, in which the Phase 2 study and just how the stem cells might work are explored. We’ll also talk about some of the other research currently being conducted in the Tisch Center’s laboratories.

Monday, February 5, 2018

Can A 100-Year-Old TB Vaccine Stop MS, Diabetes, and Other Diseases?

If I told you that a century-old vaccine – initially developed to combat tuberculosis – now appears capable of stopping or slowing multiple sclerosis, type I diabetes, and other autoimmune diseases by changing the workings of the immune system at the genetic level, would you think I’ve finally gone off the deep end? Well, hold onto your hats, or hair, or whatever else may be sitting on top of your head because the truth is out there (yes, I’ve been binge-watching episodes of The X-Files), the ramifications of which could change the treatment landscape for many hideous diseases.

I recently attended a presentation given to a group of neurologists and MS researchers by Dr. Denise Faustman (click here), a Harvard University medical researcher. Dr. Faustman is at the forefront of research into the Bacillus Calmette-Guerin (BCG) vaccine and in early trials has shown that the vaccine is capable of restoring dysfunctional parts of the immune system in patients with long-standing type I diabetes (click here). Dr. Faustman is currently conducting a phase 2 trial on long-term type I diabetics, with hopes of reporting results this summer.

Other studies have shown that BCG can alter the course and severity of multiple sclerosis (click here), and ongoing studies around the world indicate that the vaccine could have similar effects on a wide range of autoimmune diseases (click here), including Sjogren’s disease, fibromyalgia (click here), and immune mediated allergies. The vaccine is also the preferred treatment for a common type of bladder cancer (click here) and there are indications that BCG may dramatically reduce the incidence of leukemia in children (click here). It is even effective as a treatment for leprosy (click here)!

The BCG vaccine was developed at the beginning of the 20th century by two French scientists, Albert Calmette and Camille Guerin, work for which they were nominated for the Nobel Prize in 1928 (click here). Spurred in part by the observation that milkmaids appeared to develop tuberculosis in far lesser numbers than the general population, the two scientists developed the BCG vaccine using live but very weakened bovine (cow) tuberculosis bacteria, which makes cows sick but isn’t infectious in humans. The vaccine was first used in 1921 and although it ultimately proved to be only 20%-50% effective its use soon became widespread. It remains the only vaccine for TB and is still used extensively throughout Third World countries where TB runs rampant. The BCG vaccine is on the World Health Organization’s List of Essential Medicines.

At that time of the vaccine’s development, tuberculosis was epidemic and deadly. In the 1800s, TB caused about 25% of all deaths in Europe (click here). The disease, commonly called “consumption” back in the day, is highly contagious and has been infecting mankind since antiquity. Signs of TB have been found in human skeletal remains dating back millennia, even into prehistory. Before the Industrial Revolution and the beginnings of modern medicine, folklore had it that tuberculosis was caused by vampires. My recent X-Files binge tells me not to completely discount this theory.

BCG effect on MS
(click to enlarge)
Fast-forward to the 21st century, and modern scientists are discovering that the potential uses of the BCG vaccine go far beyond the treatment of TB. A phase 1 trial conducted by Harvard’s Dr. Denise Faustman, demonstrated that multiple injections of the vaccine given to patients with long-standing type I diabetes – an autoimmune disease – produce major changes in the immune system, restoring some back to normal, though a full cure and restoration of normal blood sugars has not yet been reported (click here). Italian researchers, using the same multiple BCG vaccination approach and the same potent strain of BCG, have demonstrated that patients given the vaccine after their first MS attack are up to 50% less likely to develop full-blown multiple sclerosis than similar patients not given BCG (click here), and that those who are eventually diagnosed with multiple sclerosis experience a more benign disease course. Click on the graphic to the left for a visual representation of BCG's effects on MS. Further studies are expected to explore whether aggressive treatment with BCG may temper or stop already established MS.

In addition, early studies indicate the vaccine can protect against allergic asthma (click here).  Retrospective studies have demonstrated that BCG may protect against a range of childhood cancers (click here). Other studies have shown that children infected with human tuberculosis bacteria before the age of seven have an extremely low incidence of developing multiple sclerosis (click here), hinting that the TB bug changes the immune system profoundly, and may impact a range of diseases.

The above benefits, as significant as they are, may only scratch the surface of BCG’s potential. The vaccine appears to work by altering the workings of the immune system at the genetic level (click here). Because it works on the genes themselves, the effects of the vaccine are long-lasting, and the vaccine's effectiveness appears to increase with time. Thus, a set of two or three vaccinations with BCG may offer robust defense against a wide variety of the autoimmune diseases that are now becoming epidemic in developed nations.

Evidence of Hygiene Hypothesis
(click to enlarge)
Tuberculosis is caused by a type of germ called mycobacteria (click here). The human immune system evolved in the presence of mycobacteria, which have been found in the bones of 70,000-year-old cave dwellers (click here). Over the last 40 or 50 years, though, as the developed world has become increasingly focused on hygiene and cleanliness, mycobacteria have been largely eliminated from the populations of First World nations. At the same time, autoimmune diseases and allergies have become epidemic in the same regions (see graphic to the right). The “old friends” or hygiene hypothesis (click here) suggests that the absence of the bugs that were our evolutionary companions has led our immune systems to go haywire.

Think of it like this: one spouse in a long married couple that first met in grade school suddenly exits the relationship. The remaining spouse is confused, disoriented, and likely to behave in unpredictable and perhaps self-destructive ways. According to the old friends hypothesis, this sort of disorientation in the immune system is driving a startling rise in diseases such as MS, lupus, diabetes, and fibromyalgia, all of which were much rarer even just 50 or 60 years ago when mycobacteria infections in humans were still common worldwide. Since BCG reintroduces mycobacteria into the body, it may help restore balance to immune systems that evolved with constant exposure to such bacteria.

Unfortunately, a variety of factors are hampering research into the benefits of BCG. Modern studies exploring the use of the vaccine to combat autoimmune and other diseases are still in their early stages, and many questions remain. The vaccine is manufactured using live but inactive bacteria, meaning its potency varies depending on the manufacturing facility. In her type I diabetes studies, Dr. Faustman uses a very potent version of the vaccine manufactured in Japan which is not available in North America. In fact, BCG isn’t available anywhere in North America, as the last BCG factory in the region stopped production in 2016, due to manufacturing issues and the low profit potential of the drug (click here). Additionally, queries regarding the number of vaccinations needed for full potency as well as the most optimal methods of safely introducing BCG into the human body are still to be answered.

The most significant impediment to the development of BCG as a therapy for autoimmune and other diseases, though, is a severe lack of funding. Since the drug is nearly a century old and quite cheap (single doses cost pennies in Third World nations) there is very little to incentivize the for-profit medical establishment to get behind the research. The reasons for this are myriad, but boil down to the obscene fact that all too often profits take precedence over patients in our current twisted model of medical research, which is more often propelled by the drive for ever-increasing revenues than by scientific imperative. Many potentially paradigm-shifting therapies like BCG have been left to die on the vine simply because they lack blockbuster profit potential. MS and diabetes have become mega industries generating yearly revenues of $25 billion each, creating a status quo that discourages disruptive innovation. We can’t kill the geese that lay the golden eggs, now, can we?

Research into the BCG vaccine holds tremendous possibilities for fundamentally changing the treatment landscape for a wide variety of terrible diseases that are being seen with dramatically increasing frequency, including multiple sclerosis. In a perfect world, or even a less imperfect one, massive resources would be devoted to investigating BCG and other treatments that hold great promise but little profit potential. Instead, innovative researchers like Dr. Faustman and her colleagues are left to work in the shadows while a seemingly never-ending stream of “me too” drugs are brought to market, fueling massive industries devoted to treating diseases, not curing them.

If only a fraction of the monies spent developing blockbuster drugs that keep patients perpetually dependent upon them were dedicated instead to seeking cures or researching innovative therapies like the BCG vaccine, modern medicine and the patients who find themselves stuck in the belly of the beast would be much better served. As they say in the X-Files, the truth IS out there. And it may just be hiding in plain sight.

Here’s a terrifically informative video of Dr. Faustman giving a presentation on her work. Definitely required viewing:

On a completely different note, I was recently interviewed for an article that appeared in The Accelerated Cure Project's latest newsletter (click here). For those who might be curious about what I actually sound like, the piece includes a link to the audio of our original interview. God, I hate the sound of my own voice, and I think it may just be impossible to say “um” and “you know” more than I do during the interview…

Monday, January 15, 2018

Some Wheelchair Kamikaze Film and TV Recommendations

Dealing with multiple sclerosis, especially as it advances, can be an all-encompassing, overwhelming pain in the buttocks. We all need our diversions and these can be increasingly hard to find as the disease diminishes access to the outside world, especially during the winter months when wonky limbs and overwhelming fatigue can make it almost impossible to get outside without assistance. Thankfully, in this age of streaming media on electronic gizmos of all shapes and sizes, there’s a seemingly infinite universe of high-quality films and TV shows available for the watching, so watch I do. Nothing like losing yourself in a great flick or binge-watching an engrossing TV series to temporarily keep thoughts of the MS beast at bay.

Last year I posted a list of some of my favorite, somewhat obscure films (click here). I figured it’s about time to put together another such inventory – especially since I’m not in the mood to write yet another essay excoriating the MS status quo or plumbing the depths of my own experience with the disease. Time enough for that later, but for now here’s a list of some of the movies and TV shows I’ve been keeping myself occupied with of late.

There are a few oldies but goodies sprinkled in here, as well as some foreign fare. For those who are put off by the prospect of subtitles, I’d urge you to give at least one or two of these suggestions a try, as I’ve found that watching foreign flicks is like virtual tourism. I love soaking in the little details and differences of life in foreign lands, from local social customs and dress to such esoterica as the differences in light switches and bathroom fixtures, even if it's only by way of TV screen. Nothing like taking a short trip to Paris or Belgium while sitting in your wheelchair, stuck in your living room wearing nothing but your skivvies. And I promise, if what you're watching is good enough, before you know it you won't even realize that you're reading subtitles.

Please feel free to comment on any of my selections or to supply a few of your own in the comments section of this post. Enjoy…


The Grand Hotel Budapest – This quirky gem by director Wes Anderson is a sheer delight. A visitor to a long in the tooth but once grand hotel is told an enchanting tale of the venue’s glory days by a stranger he meets in the lobby. The film swoops and swerves as it follows the adventures of the hotel’s once legendary concierge and his sidekick lobby boy as they traverse a fictionalized and fantasized Europe in the time between the two world wars, getting mixed up in all sorts of absurdist escapades along the way. This is kookiness and eccentricity at its best, filled with heart, sentiment, tremendous humor, and a sense of pure revelry. Available to rent from Amazon video.

Boy – from the same director as Hunt for the Wildepeople (Taiki Waititi) – which I recommended in my last list – this charmer from New Zealand is the coming-of-age story of an 11-year-old Michael Jackson obsessed Maori boy as he gets to know his miscreant father, who is just back from a stint in jail. Set in 1984, the film is original and whimsical, heartfelt and idiosyncratic, as we follow the father’s comically obsessive search for ill-gotten money he buried in a field years before, employing the help of his inept outlaw gang and his son’s friends and acquaintances. Included are priceless reenactments of some of Michael Jackson’s most famous videos, including this Maori version of “Thriller.” Available for streaming on Amazon Prime…

The Swimmer – This all but forgotten 1968 Film is perhaps more pertinent today than when it was made 50 years ago. Starring the great Burt Lancaster as what initially seems to be a gregarious and successful ad man, The Swimmer follows this character as he makes his way across a wealthy Connecticut suburb one beautiful summer day, on a quixotic quest to swim home by stopping in his neighbors’ backyards and doing one lap in each of their pools. At each stop, the reality of the character is slowly revealed, his initial polished veneer stripped away bit by bit. The film explores the shallowness of a consumerist society that defines the value of a human being by the material goods they possess and shines a light on the lies we tell to others as well as the ones we tell ourselves. Based on a John Cheever short story, some of the cinematic techniques used seem a bit dated now, a half century after the film’s production, but the themes it explores and Lancaster’s stellar performance transcend any such quibbles. Available for rent on Amazon video.

Let The Right One In – this Swedish film focuses on a bullied 13-year-old boy who is befriended by his new neighbor, a mysterious 12-year-old girl who he only sees at night, and who sometimes smells a little funny. Okay, I’ll let the cat out of the bag – she’s a vampire, but I would hardly label this a vampire film. Let The Right One In tells a story of affection, devotion, alienation, and manipulation in a stark and intimate way. Although there is some blood spilled along the way, the story is more existentialist than horrific. Beautifully shot and directed, the film is set in a desolate and icy town outside of Stockholm. This is a cerebral film that leaves plenty of room for interpretation and is one of those movies that sticks with you for quite a while after viewing. Let The Right One In was remade in an English version as Let Me In, which is also quite good but a bit more straightforward in the telling than the original. I personally prefer the Swedish version, but the two films are good enough to warrant watching both. Start with the original Swedish version, though, unless you just can’t stand the thought of subtitles. Both films are available for rent on Amazon video.

TV shows:

Broadchurch – this magnificent British crime drama features a big-city police detective with skeletons in his closet who finds himself reassigned to a small coastal town in northern England. The show is three seasons long, with eight episodes per season. Seasons one and two deal with the murder of a young boy and its aftermath, which threatens to tear all involved and the town itself apart at the seams. Season three focuses on the investigation of a sexual assault, while the principles still contend with the emotional fallout of the crime investigated in the first two seasons. This show is about as good as it gets, with acting, tone, and content all achieving perfect pitch. The characters are intricate, the writing spot on, and the scenery itself breathtaking. I can’t recommend Broadchurch highly enough. Available for streaming on Netflix.

Hotel Beau Sejour – I absolutely loved this Belgian show. Kato, an appealing young woman, wakes up to find her own murdered body in the bathtub of an old hotel undergoing renovation. Confused and disoriented, she makes her way back to town and slowly realizes that she is indeed dead, but that five of her friends and family can still see her. Determined to unravel the mystery of her murder (she can’t remember anything from the night of her death), she sets about trying to assist in the solving of the crime as best a ghost can. As Kato struggles to uncover the truth, she discovers the secrets and deceptions of nearly all involved, secrets that even those who hold them are loathe to confront. I found this 10 episode series to be addictive, so much so that binge-watching seemed to be the only option. An added bonus, for me at least, is that the characters speak Flemish, a language I’d never before heard spoken and which seems to be a mix of Dutch, German, French, and English. Again, I’d urge not to let the prospect of subtitles deter you. Though there are some lapses in logic – why does a ghost need to wear a helmet when riding a motorbike? – this is a terrific show. Available for streaming on Netflix.

The Returned – this French series is spooky and disconcerting in the best possible way. Set in a remote French town that has suffered through a series of past tragedies, the community is once again rocked when some of its dead start returning in seeming perfect health and at the same age they were when they died. They have no sense of their own deaths and have no idea how or why they were resurrected. Shot in muted colors that perfectly match the mood of the series, The Returned explores the wounds of what might have been, and whether or not that those who were once given up for lost can ever truly be fully recovered. Throw in the resumption of a series of killings that had stopped years before, and you have the makings of an engrossingly moody Gallic meditation on the circle of life and the nature of good and evil. The show is two seasons long, eight episodes per season, and is available for streaming on Netflix. (Please note, this series spawned several remakes, including an absolutely horrendous American TV network version and a word for word English translation of season one that aired on the A&E network. I haven’t seen the latter, but only one season was produced, so the A&E version does not come to any resolution. This version is also available on Netflix, though, so please make sure to pick the original French version, which was titled Les Revenants).

Glitch – this is an Australian take on The Returned. It’s a markedly different show than The Returned, absent the moodiness and mystery of the original, but is excellent in its own way. Glitch doesn’t spend much time contemplating the metaphysical ramifications of resurrection, instead placing its focus on the personal histories of seven folks who have clawed their way out of the cemetery of a small western Australian town – most are from different historical periods – and on the science that brought them back. There are some shady characters about, most connected to a suspicious pharmaceutical company located in the vicinity. Each of the resurrected has a fascinating backstory, which they only start remembering in pieces. Much of the show is driven by each character attempting to put together their own personal history and the circumstances of their death. As the show progresses, it becomes more bittersweet than spooky and evolves into more of a thriller than a study in horror or philosophy. Despite its differences from The Returned, both shows had my wife and I hooked early on. Glitch is available for streaming on Netflix, but be forewarned that to date only two seasons have been produced, with the third seemingly still up in the air. The show doesn’t come to any hard resolution, but I found it so enjoyable that it warranted a mention regardless.

Hope you enjoy some or all of these picks. As mentioned earlier, please feel free to use the comments section to voice your own opinions or offer some viewing suggestions for fellow WK readers.

WHEELCHAIR KAMIKAZE SNEAK PREVIEW: I recently conducted a 90 minute interview with a naturopathic doctor who specializes in treating MS patients. The interview is jampacked with lots of important information and actionable ideas. I should be posting the first part sometime in the next several weeks – I have a lot of transcribing in front of me – and I think this interview will be of great value to WK readers.