Dr. Richard S. Bedlack, MD, PhD, MS
Duke University School of Medicine
Interview Date: November 19, 2014
Dr. Bedlack explains ALSUntangled, a program he started to give ALS patients scientific reviews about alternative and off-label treatments. About 50% of patients with ALS try at least one of these treatments over the course of their illness; maybe something they heard about through friends, family, or the media. He shares some “red flags” for treatments that are not likely to work. ALSUntangled helps to educate and empower ALS patients to make educated choices about their care. He encourages patients to be involved in research studies as well as clinical trials to increase the knowledge and lead to a cure for ALS.
ALS Crowd Radio Show with Dr. Bedlack
Seth: Hello and welcome to episode 9 of ALS Crowd Radio. I’m your host, Seth Christensen, here with Amy Christensen. And we have the honor today of having as our guest, Dr. Richard Bedlack of Duke University. Amy?
Dr. Richard Bedlack grew up in a small town in central Connecticut. He went to college at William and Mary in Virginia, then back to Connecticut for his MD and PhD in Neuroscience at UConn. Finally, he came to Duke where he completed his Medical internship, Neurology Residency, Neuromuscular Fellowship, and Masters in Research Science.
He started the Duke ALS Clinic, the Catfish Hunter ALS Clinic at East Carolina University, and the Durham VA Tele-ALS Clinic. He is currently a tenured Associate Professor of Medical Neurology at Duke and Director of the Duke ALS Clinic and the Durham VA Tele-ALS Clinic. He has won awards for teaching and patient care, including best Neurology teacher at Duke, Health Care Hero, Strength Hope and Caring Award, America’s Best Doctor, the American Academy of Neurology’s Viste Award for Patient Advocate of the Year, and the ALS Association’s Rasmussen Award for ALS Advocate of the Year.
He has received research grants, participated in clinical trials, and published more than 70 articles. He is past Chair of the North American ALS Research Group and current leader of the NEALS Patient Education and Advocacy Committee, and the international ALSUntangled program which utilizes social networking to investigate alternative and off-label treatment options for patients with ALS.
He lives in Durham North Carolina with his wife, Shelly, and two mischievous kittens.
Seth: Welcome. Dr. Bedlack. Thank you for joining us today.
Dr. Bedlack: Well, thank you, Seth, and thank you, Amy for that nice introduction. It’s great to be with you.
Seth: Hopefully those two mischievous kittens are behaving.
Dr. Bedlack: Never, never.
Seth: We appreciate your time today and know that we have a lot of folks interested in hearing your insights so we’ll jump right into it. Amy?
Amy: Yes. Callers and listeners, we would love to hear your questions today. Please call in to ask questions to Dr. Bedlack at 516-590-0362 and push number 1 to indicate that you have a question today.
Seth: Thank you, Amy.
Dr. Bedlack, we had the honor of meeting you recently and receiving your insights and wondered if you wouldn’t mind sharing the overall focus of your research.
Dr. Bedlack: Yeah! Well, Seth, it was my honor to meet you and Amy as well.
My research really is focused on trying to find new treatments that help people with ALS and overall, trying to speed our journey toward a cure for this disease. And so that kind of falls into three categories. One is I do clinical trials. Some of those trials are investigator-initiated, meaning they happen only at Duke. Some of them, I’m an investigator for a multicenter trial like a phase II trial for example, the Cytokinetics trials that were going on or even a big phase III trial like the dexpramipexole study.
Second group of things I do involves reviewing alternative and off-label therapies and by that, I mean treatments that are being proposed for use in ALS, may be advertised as slowing or stopping the disease, without a lot of mainstream evidence for those. So things like coconut oil and marijuana for example.
And in the third sort of research that I do is I’m trying to actually build an army of advocates, patient advocates for research and that’s where I met you and Amy at one of the clinical research learning institutes that I helped create and run through the North East ALS Consortium. And the importance of that is just trying to make sure that there aren’t any patients who don’t know what their research options are so we want the graduates of this program to go and speak at support groups and fundraisers and to go on Facebook and spread the word about studies that are open and make sure that people don’t have any misconceptions about research studies and make sure that funders always realize how important ALS research is.
Seth: Thank you for that overview. We have marketed today’s show as investigating alternative ALS treatment. But for one moment I want to touch on your third area, training patient advocates. Why is this important in the whole ALS ecosystem?
Dr. Bedlack: Well, Seth, one of the things that a lot of people probably don’t realize is that enrollment in ALS research studies is surprisingly low. So somewhere between 5% and 10% of patients who have ALS ever enroll in a research study and only about two patients per site per month are enrolled in multicenter trials.
So for example, at Duke, I might see 40 patients in a month and only enroll two. And so the questions are why is enrollment so low? It’s such a tough disease, we have some treatments to offer but nothing that stops or reverses the disease. You think people would want to sign up for research study in droves.
Well, there’s lots of reasons why people don’t sign up. One reason is that patients may not know that they have an option for research. Another is that they may have misconceptions about a research study. For example, one thing that I’ve heard from patients when they turn down a research study is they’ll tell me, “I feel like if I sign the piece of paper that informs consent, that I’m basically going to be a guinea pig and you can do whatever you want to me”, and that’s a misconception. And I understand why it happens because in the past, in the United States, there was research like that, there were things done to patients in trials without their knowledge. But nowadays, there’s a ton of oversight, there are tons of laws that protect patients from that happening again.
And so those kinds of misconceptions and those kinds of missed opportunities to get people in research, we really can’t afford that as a field. We’ve got to try to boost our enrollment rates so we can get through these studies faster and ultimately get to a cure for ALS faster.
Seth: Thank you. We as a patient community need to understand that and I think your work in training patient advocates is central to that. So thank you.
Dr. Bedlack: Pleasure.
Seth: Turning our focus to today’s topic now, investigating alternative ALS treatments, could you explain to us what ALSUntangled is?
Dr. Bedlack: Yes. So ALSUntangled utilizes social networking to try to provide a scientific review for alternative and off-label treatments for ALS. And again, alternative and off-label treatments would be things that somebody is advertising for use in ALS without mainstream data, so without phase I and phase II and phase III clinical trials. Again, some examples would be things like coconut oil and marijuana.
Seth: And why did you start this effort?
Dr. Bedlack: Well, so I noticed, Seth, when I started the Duke ALS Clinic in the year 2000 that a lot of my patients were trying these alternative and off-label therapies and it turns out when I looked in the literature, more than 50% of patients with ALS would try at least one of these over the course of their illness. And it seemed to me that there were three ways that this situation was handled by doctors in the ALS field and I’ll divide those into paternalism, autonomy, and shared decision making.
So a paternalistic way to handle this would be to say to your patients as if you were their parent, “That’s really not a good idea, you shouldn’t do that, it’s never going to work.” The problem with that is first of all, it’s not very respectful, and second of all, it’s dishonest. I mean we don’t know whether these things might work unless we actually look into them. You can’t just look at something and know that it won’t work, you have to actually do a little bit of research on it.
The second way we handled it was through autonomy where we’d say to the patient, “Okay. Well, good luck with that. Let’s turn our attention to the things that I can offer you in the clinic.” The problem there is that the patient is actually relying on the doctor I think in many cases to utilize their many years of training and experience to help them sift through whatever data is available on that thing and make an informed decision.
And so the final model was shared decision making where we do exactly that. The patient would ask us about a particular thing, maybe a stem cell clinic in China and we’d spend a few weeks researching it, trying to find out exactly what they were doing, trying to find a way to talk to the person who was in charge, trying to find patients who went there and find out what happened to them, and then get back and actually tell the patient what we found and make a recommendation based on that. And that’s great. Patients like that, doctors really enjoy that but the problem is it takes a ton of time. And the other problem with that is that next week, when someone down the street at another ALS clinic asks the same question to their doctor, they have to reinvent the entire wheel again.
So we created ALSUntangled to engage in what we call shared decision making. So we do all these reviews by committee and we publish the results so no one has to do the review again. We can all kind of point to that and say, yeah, that’s kind of what the field thinks about this particular alternative and off-label therapy.
Seth: So I am out on the website ALSUntangled right now and it appears we have completed 26 formal reviews and have, wow, quite a few under way.
Dr. Bedlack: Yes. That’s the mode of the challenges is that there’s a lot more of these than I ever realized and so we certainly want to put them all on a list and we’ll get to them one by one. But this so far has been a sort of a part time thing that most of us do nights and weekends. There’s no like protracted time, there’s no funded time to do this so this is a labor of love, if you will. We don’t crank this out nearly as fast as we’d like to.
Also the way that we do this, it’s challenging. This is not traditional research where you know exactly there’s a blueprint and exactly how to do a good mouse study or exactly how to a phase II trial. A lot of this stuff, we’ve kind of have to sort of pave the way and the whole process of doing research like this.
Seth: Let’s step for a minute into that process. You use Twitter to decide which studies to engage in, correct?
Dr. Bedlack: Yes. So there are three parts to this program: inputs, reviews, and outputs. The inputs come by any means necessary. So most of them now, as you pointed out, are coming from Twitter. We average about a tweet a day. Some of them come through email so my email is all over the internet. Some of them come from emails by my colleagues, like a patient in their clinic asked them face-to-face about something and they’ll email it over to me and it gets on the list that way.
And then there’s the reviews themselves. So we’ve long had a sort of standard operating procedure for doing these and it starts with making multiple attempts to contact the person that’s selling this particular AOTs so make sure we understand their side of it. We try to get any kind of materials they’re using to advertise this, figure out what the claims are. We do a PubMed search. PubMed is a database that has scientific publications to find out if there’s any scientific paper and a peer review journal about this thing. We do a Google search which is where we find a lot more of the information we look at and that’s where you find things like blogs.
We do a poll of all the ALSUntangled investigators and there are now 94 ALSUntangled investigators from across ten countries. The purpose of the poll is to find out if any of us take care of patients who’ve tried this and if so, what happened. We look at big shared database called PRO-ACT and we try to see if anybody in that database — and there’s almost 9,000 patients in that database — if anybody has ever said they were trying one of these things and then what did their outcome measures look like before and after they tried this.
We look on the website PatientsLikeMe and there we can find information about subjective outcome measures that patients input themselves. And then we try to visit the clinic, review the infrastructure of the clinic, interview people that are there, look at the medical records. Most recently, we’ve actually instituted something even one step beyond this which is something called the Table of Evidence. So we Crowd-Source this because again, there was no precedent to doing something like this for looking at this kind of data. And we decided that in ALSUntangled, we’re really looking at four types of data: mechanistic plausibility, preclinical data, case reports, sometimes trials, and then data on risk.
And so in those four categories, we’ve come up with an ordinal system for grading each AOT on each of those categories. So for example, under mechanistic plausibility, you’d get a grade A if you showed in a peer-reviewed publication that whatever is that you’re selling could act on a relevant mechanism in people with ALS; and you’d get an F if this thing that you were trying to sell violates known laws of physics and biology like for example, energy healing. We’d have to rewrite the textbooks if that existed. Now, it might work but still, as of right now, you’d get an F grade for mechanism because that mechanism is not recognized by science.
I think this is going to help us in a lot of ways. One is it makes it a lot transparent what we’re doing. Each one of our reviews from now on will get letter grades in all these categories. Second, it allows us to quickly update a review. So for example, the Deanna Protocol. When we first reviewed them, I think it was a little over a year ago, they didn’t have any animal data. Now they have one animal study, one small animal study so they get an upgrade there. And third, hopefully this allows people in other diseases to do something similar to what we’re doing because I’ve heard from other people like in MS and Parkinson’s that they would love to do something like this but it’s hard to get started. So hopefully, this provides a nice blueprint for how to get started reviewing evidence on AOTs.
Seth: Fascinating! Now, who of these, the 94 reviewers, who comprises that body? Is it international, is it only Western-trained, is it more on them?
Dr. Bedlack: So there are people from ten different countries, they’re mostly clinicians but some of them are like basic scientists, for example. And so the countries that are represented include United States, Canada, Ireland, Israel, Spain, Thailand, Sweden, Poland, France, and Russia. So we wanted this to be international for a lot of reasons but partly because some of these clinics are in faraway places and so if we’re going to try to visit clinics, it would be great to have people all over the world that are part of our team so it would be easier for them to get in there and review the clinic.
Seth: Is there an oversight board that decides who is in, is not on that review committee?
Dr. Bedlack: We don’t really have any kind of oversight board. So if you have a history of doing an ALS research, you send us an email and say, “Hey, I’d like to be in the ALSUntangled.” We do just a quick literature search to find out has this person done anything related to ALS research and if so, you’re in. We don’t have a big vetting process but at the same time, we do want to have some history of engaging in ALS research to be able to be part of the team.
Seth: We love it! And now, are you funded by anyone?
Dr. Bedlack: Right now we have a small amount of funding from the Motor Neurone Disease Association and what that funding does is it allows us to keep our website up to date. I don’t know much about building websites or keeping websites up to date so I have to hire somebody to do that. So that’s basically what the money pays for right now.
We’re hoping maybe to get a grant in 2015 that would allow somebody like myself to spend half-a-day doing nothing but ALSUntangled so that we could get through this list of over 130 open reviews a little faster.
Seth: Thank you. We will ask at the end of our show how people can donate and support this amazing method for researching alternative treatments.
Dr. Bedlack: Oh, thanks, Seth.
Seth: We’re huge fans of out-of-the-box thinking and think you are as out-of-the-box as we’re comfortable with.
Dr. Bedlack: I appreciate that.
Seth: Amy, could you remind callers of the number.
Amy: Yes, we have several callers online now. If you’re just joining us, please call in to 516-590-0362 and push number 1 to indicate that you have a question for Dr. Bedlack when we come to that point.
Seth: We realize that callers get nervous but we promise Dr. Bedlack will not chew you out on the air.
Dr. Bedlack: Never. Never.
Seth: All right. Dr. Bedlack, could you share a couple of your favorite reviews and subsequent findings?
Dr. Bedlack: Yeah, I’d be happy to.
There’s been some real surprises to me over the five years that I’ve been running this program. The first group of surprises deal with the people that are actually selling these AOTs. When I first started this, I had the impression that a lot of them we’re going to be kind of like the old Wild West snake oil salesmen just out to make a buck. And we certainly have found some of those, the most famous of those is actually a person named Dr. Larry Stowe. You can read more about him on the 60 Minutes webpage, they actually did a whole story about him called “21st Century Snake Oil”.
But surprisingly, there are many more people out there that I call true believers that are selling these things because they really believe that they work, they really believe that they’re helping people. And in fact, some of these folks are really good doctors, like the ALS community of physicians can learn a lot from the bedside manner of some of these folks. I’ve been to some of their clinics and I’ve watched them interact with patients and I’ve interviewed patients afterwards and ask, “How did you get here?” like “How did you get in this chelation clinic?” Many times patients say, “We started in a mainstream clinic but it was all gloom and doom. Nobody gave us any hope, they just wanted us to sell our living wills and people didn’t want to hear about our ideas and even when we would ask a question by email or telephone, it would be many days or sometimes weeks before we’d get an answer back.” And some of these folks that run these alternative clinics, well, they’re the most optimistic people I’ve ever seen. They’re incredible cheerleaders, they’re very respectful of their patients’ ideas and they’re very responsive.
I remember being at a chelation clinic in Hilton, had to be in late at night because the doctor told me that every night when clinic finished, he made sure every message was answered before he went home for the night. And I just think those are three key things that we need to be as ALS clinicians: optimistic, respectful, and responsive to our patients.
And then the other thing, Seth, are some of the actual treatments themselves. Again, when I first started this program, I was very skeptical that any of these things were going to be very useful. And certainly we have found a lot of things out there that are bogus. I can give the listeners some things that these share in common, I call these the red flags, things to watch out for if you’re thinking about a particular alternative therapy.
First of all, anybody who’s advertising something as dramatically effective or a cure for many of the world’s worst diseases — 20, 30, 40, 50 of the world’s worst diseases — you have to be a little skeptical of that. Like why would this person who says that they can cure 40 of the world’s worst diseases be practicing in a strip mall in India next to a Kentucky Fried Chicken? They should be one of the most famous wealthy people in the history of Medicine, it just doesn’t make sense.
Anything that’s advertised as perfectly safe, it doesn’t make sense. Nothing’s perfectly safe. If you’re in a stem cell clinic and you’re doing blood tests, bone marrow biopsies, and spinal taps and you write that you’ve seen 2,000 people and no one’s ever had a side effect, that’s just not possible. Someone’s going to have bruising, someone’s going to have pain, someone’s going to have an infection when you break the skin 2,000 times.
Anytime you’ve got a clinic where there’s no oversight; anytime you’ve got a clinic that’s run by somebody who doesn’t have any credentials; anytime you have a clinic where they’re not asking you to sign any kind of consent form so you’re not actually seeing in writing what the potential risks and benefits are. And maybe worst of all, anytime you have a clinic where they have no interest in following you after you pay and get the treatment — that’s a problem. If nothing else, we need to be able to track what happened to the people when they get these things. And if you’re at a clinic where they want to charge you a bunch to give you something and then never want to see you again, that’s probably not a very legitimate clinic.
But you know, Seth, some of these things actually look like they might be useful and probably do warrant further study. So just to tell you quickly about some of those, there’s one called AIMSPRO also known as hyperimmune goat serum. I won’t talk too much about that because the company, Daval International, is actually going to do its own follow up studies on that compound. There’s a supplement called GlutaMAX which is a combination of vitamins and flavonoids which are antioxidants. And there’s some very interesting anecdotal data to support that that seems to be reasonably safe and reasonably inexpensive.
Lunasin which is my most recent ALSUntangled investigation and that’s one that I personally am very excited about, excited enough to be launching a trial of it in 2015. It’s a peptide from soybeans. It’s taken orally and it supposedly has histone-altering properties. So if you alter histone acetylation, you change the pattern of genes that are on, possibly toward a more protective pattern. It’s also reported to have anti-inflammatory and antioxidant effects. And what’s very exciting about that is I’ve got one validated case of a person whose records I have. Three different neurologists diagnosed him with ALS, I believe he has ALS. Hes dramatically improved over the course of one year on this supplement so this is something that I call “a validated ALS reversal.” And when we find validated ALS reversals, whatever it is that they tried, we need to try that in more people. And we’ll figure out why it worked later but first we have to figure out if it’s working. And so that’s why I’m picking that one first because that’s one of the more dramatic cases I’ve seen.
And then lastly and the strangest of all, there’s something called fecal transplants. And Seth, when I first heard about this from one of our ALSUntangled tweets, I thought maybe there was a misspelling. I thought it was fetal transplants but no, fecal with a C literally is what it sounds like. Taking the stool from a person without a disease, making sure there’s no infection in there and then putting it into the colon of a person with a disease. And what’s the rationale here? Well, within all of us, there’s a family of bacteria in our gut called the microbiome and there’s pretty good evidence now that when the microbiome gets altered, when one particular bacteria overgrows, it can cause human diseases. And the best evidence is diseases of the gut like for example, clostridium difficile infection or even Crohn’s disease. Fecal transplants is now a mainstream treatment for those. It turns out there is a bacteria, a clostridial species that can secrete a toxin that can kill motor neurons. It can actually get out of the gut, cross the blood-brain barrier and kill motor neurons.
So wouldn’t it be interesting if there’s a subset of people with ALS who actually have their disease because they have an altered microbiome and if that were true, then a fecal transplant might actually stop the disease in them. So I’m hoping that at some point, we’ll see folks actually study the microbiome in people with ALS and see if there are subsets and if there is a subset with this clostridial species, try a fecal transplant and see what happens.
Seth: Well, I’ll add that to my list of favorite, non-favorite things to try.
That was an amazing list of your top candidates. As an ALS patient, you hear all the time the disease is very heterogeneous and we don’t know what causes it and how it proceeds so differently in different people. As the effect of diminishing our confidence in anything that we are regarded to try, thinking that “Wait, I may be different”, can we rely on scientific studies that are seeking a treatment there for all ALS patients or do we have to filter those through our own perception of our personal disease?
Dr. Bedlack: So I don’t think that right now we’re smart enough to know how to subdivide patients with ALS and that’s part of why there’s such an emphasis on finding biomarkers that might be able to tell us about different pathophysiologies in different patients. That’s one of the reasons I love that microbiome study. A microbiome is a biomarker that might lead you to a different cause for that person’s ALS and a completely different treatment. There’s got to be those. Those are going to happen. There’s going to be a genetic, there’s going to be imaging biomarkers, there’s going to biomarkers in the serum in the CSF, it will all happen over the next few years.
But until then, I think the best we can do is continue to do trials the way we’re doing them but look within our trials for groups of patients that might have responded. Don’t just give up on the trial when there’s no different overall between the treated and the placebo group. Look to see like the NP001 folks if there might be a subset of folks that actually responded and then try to figure out what’s different about them later.
Seth: Incredible! The biomarker study you mentioned, is it happening at one place or everywhere?
Dr. Bedlack: There’s a lot of different biomarker studies going on now and one of the really cool things is that for the first time, we’re really starting to share data. Not only are we putting data into the PROACT database, we’re putting data into the Neurobank database. We’re starting to require that funded trials use something called a global unique ID so that the patient basically would have one ID that they would carry with them no matter what study they ever participated in.
And that’s the kind of stuff we really need to do to beat this disease. We need to be able to share data across the whole world, that we get giant amount of information on one place.
Seth: Thank you. Amy?
Amy: Yes. Callers, the number to call in to ask questions is 516-590-0362 and press 1 for any questions for Dr. Bedlack.
Seth: Thank you. We’ll pause on this topic for a moment, Dr. Bedlack, and ask, stepping back, what other trials and research are you currently involved in?
Dr. Bedlack: Yes. I just found out that I’m going to be part of something called the CReATe Consortium. This is a rare disease clinical research network that’s sponsored by the NIH. And CReATe is actually an acronym, it stands for Clinical Research in ALS and Related Disorders for Therapeutic Development. And our lead investigator on this is Dr. Michael Benatar at Miami. But this is going to be an incredibly exciting program that tries to bring together patients with a lot of different kinds of motor neuron diseases — so ALS, PLS, progressive muscular atrophy, hereditary spastic paraplegia, and we’re also trying to bring patients with frontotemporal dementia into this mix as well.
So we’re trying to get them into the same studies, the same databases because we know there’s going to be overlap in what’s happening in their bodies. We’re also trying to get all the different advocacy groups to the same tables. So the ALS Association, the Muscular Dystrophy Association, the Spastic Paraplegia Foundation, the Association of Frontotemporal dementia all the same table so we can figure out how to synergize and how not to have too much overlap between what we’re all trying to do. So this is exciting on a lot of different levels but it’s an entire program, it’s not just a study.
And then I’ve also got a Cooperative Study Program through the VA Medical Center which is called Cooperative Studies 567. It’s a study of a brain computer interface for patients with ALS. So this is the way for folks who’ve lost most of their movement to be able to continue to communicate and possibly even continue to surf the internet and control devices using the electrical activity in their brains with no movement at all.
And then we’ve got upcoming in 2015, a nice trial of an antiepileptic drug called retigabine. And finally, my ALS Reversals program, I’m very excited about this. As I mentioned with Lunasin, over five years in the ALSUntangled program, one of my frustrations has been that once in a while, I run into a patient that I actually think had ALS and got much better. Some of them got completely well and I’ve never had the resources to follow up and study those patients. And I think we have to.
I think when you run into an ALS reversal like the one I mentioned in the Lunasin paper, there’s a lot of different possibilities. One is they were misdiagnosed so to we want to make sure we got records on those folks. Another is that they might have had something different about them that allowed them to beat the disease. You may have seen in the news last week, there’s a group of people that have HIV and they never progressed to AIDS. And in fact, sometimes in those people when you look down the road, the virus appears to be gone and those people never got any treatment. They call those people elite controllers and there’s been a lot of debate about whether it’s worth studying them. It’s a very rare group but there’s been a small tenacious group of investigators that have been studying them. And last week, they had a huge breakthrough. They actually figured out that at least some of those people, the way they beat the disease is they have an enzyme that allows them to incorporate the retrovirus DNA into their own DNA. In other words, they kind of absorb the virus into their own DNA and it becomes part of them, it becomes non-toxic, they bind with it.
And so imagine if some of these people who have ALS and get better have something that’s genetically different about them like these elite controllers that allows them to beat the disease. We need to know what that is. We need to try to give that to other people. And then finally, it’s just possible that some of these folks that have ALS reversals get them because they actually tried something that works. And so part of this program is going to be trying to actually give whatever these ALS reversals used on themselves, give it to other people and see if we can make anyone else better.
Seth: I’m fascinated that you, more than any of our previous guests, are interested in the outlier cases. We understand the economics of going for the largest group in a rare disease community but applaud your efforts in this area.
I wonder if you wouldn’t mind sharing your X Files reference that you shared with me, how that plays a role in how you think about this work.
Dr. Bedlack: Yeah. The whole reason that I really got ALSUntangled off the ground was because of a patient and I’ll call her Samantha. The reason I call her Samantha is I kind of think of this whole program as the X Files of ALS. And for those who remember the X Files, the TV show that ran for a little over ten years here and spawned a few movies, the premise of the show was there was a guy named Fox Mulder and when he was a kid, he saw his sister, whose name was Samantha, disappear. And the way he remembered it, she was kidnapped by aliens. And of course, nobody believed him and he felt all this guilt about the fact that his sister disappeared on his watch and he spent the rest of his life trying to investigate strange happenings in hopes that he would be able to prove to people that aliens really did exist.
The patient that kind of was the index case for me was a university professor that came to see me that had a pretty clear-cut diagnosis of ALS, didn’t seem to have an cognitive or behavioral problems. And I broke the news to her, I told her about the evidence-based options that I had for her and I invited her into some of the research studies that we were doing. She said she’d be happy to take riluzole and come to clinic and do the evidence-based things we had but she wasn’t going to do research. Instead she was going to try oral sodium chloride which she had read about on the internet on Good Morning America’s website.
And so driving home that day, that really left an impression on me that first of all, that people would try this and I did the research and found out that a lot of people try it. And second of all, that even very intelligent people try this without really a very thorough investigation of the evidence. This was a Good Morning America website, there was really almost nothing on the website about the mechanism of oral sodium chloride, whether it worked as well as IV sodium chloride, what kind of harms might come to a person, where they would get it.
That’s why there is a parallel with the X Files. I really wanted to help this patient like Fox Mulder really wanted to help prove what happened to his sister, and that motivation continues. For me the motivation are the patients that I see every Monday and Tuesday, ALS Clinic every Monday and Tuesday now, and they keep me motivated.
Seth: Thank you.
Before we go to our callers, I would remind callers, you need to press 1 to get in the question queue. Last question before we open the lines, are there any other projects in ALS you are excited about and would like to mention?
Dr. Bedlack: Absolutely.
So I think there are a lot of exciting things on tap for 2015. I’m hoping that Neuraltus Pharmaceuticals can get the funding that they need to do a study of NP001. As I mentioned before, this is an intravenous drug and it acts on part of the immune system called macrophages. And what was exciting about their phase II study was they appeared to find a subgroup of patients, about 30%, who took the drug and didn’t progress at all for six months. And that’s different than the natural history of ALS where about 10% of people would be expected not to progress for six months.
There’s another company out there called Cytokinetics and they have a drug called Tirasemtiv. It’s been through several small studies. The studies were regarded as “negative” studies because they weren’t able to show a benefit on the primary outcome measure which was the ALS Functional Rating Scale. But all the studies did show benefits on muscle strength and benefits on breathing measures and obviously, those are important. So even though it didn’t affect the ALS FRS, thankfully the company has decided to go back to the FDA and try to get permission to do a follow up study where strength and breathing measurements would be the primary measures. So I think that that’s got a really good chance of being something that we can use to help patients.
And then of course, there’s the stem cells studies, Brainstorm cell and Neuralstem. Those are exciting for a lot of reasons but to me personally, the reason why they’re exciting is each of those studies has an ALS reversal. So Brainstorm has a rabbi that took that product off-label, whose ALS got dramatically better. And Neuralstem has a very well-known American patient within the Neuralstem study who had dramatic measurable improvements in muscle strength and activities of daily living.
So I think those are all things we can look forward to in the next year.
Seth: Thank you for those.
We will now go to our first caller. Caller ending in 0559, you are on the air with Dr. Rick Bedlack.
Caller: Yes, Dr. Bedlack. I will need some additional information on the Lunasin. Is that an oral medication and could you reviewl a little bit more of how it worked and potential side-effects and how someone would go about getting into your study?
Dr. Bedlack: Sure. All the information that you just asked about is in that free article that’s on our website which is alsuntangled.org and it’s the last review on the website that says Lunasin.
So this is an oral substance and it actually comes in a variety of different forms. It’s overall a peptide that comes from soybeans. And the mechanisms that it appears to have in cell cultures, it can reduce free radical production by activated macrophages, it can scavenge free radicals, it can alter the release of inflammatory cytokines from macrophages, and it can alter the pattern of histone acetylation which in turn should be able to alter the pattern of gene expression hopefully toward a more protective pattern.
So at least in cell cultures, it’s got a lot of promising mechanisms. But the main reason that I’m personally going to study this is because there’s a patient from the New England area who took a combination of products containing Lunasin, and over the course of a year, had dramatic objective improvements in his speech, swallowing, and limb strength. The supplements that he took, it wasn’t just one, it was actually a series of things. They all came from a company called Reliv and the supplements included LunaRich X capsules, something called Reliv Now®, and something called ProVantage. And again, the exact regiment that he took is in that paper.
As far as the study goes, it’s probably going to be a fairly small study. It’s actually funded by a group of patients that contributed money to our clinic. We’re thinking that it’s going to be somewhere between 30 and 40 patients. I suspect it’s going to fill up pretty fast. It’s probably going to open around March.
There’s a few benefits from being in the study of course. One of the benefits is that you’re helping us figure out if this works or not, that’s the main reason to go into any research study. But also, folks who come into this study will be able to get these products for free. The company is actually going to supply them for our study and outside the study, these are rather expensive. So to do exactly what this patient did would be about $700 a month.
This study’s going to be unusual for a lot of reasons. We’re looking for the biggest effect that’s ever been seen in an ALS research study. So most of the time in an ALS research study, we’re looking for a very slight slowing in disease progression like a 20% slowing in the slope of the ALS Functional Rating Scale for example. And when you’re looking for a very small effect in a disease that’s very noisy, you need to try to make your patients look as similar as you can at the beginning of the study, that’s why the inclusion-exclusion criteria is so narrow for research studies. You need to have a lot of patients and you need to have a control group that you also enroll at the same time and treat exactly the same way — usually a placebo group.
So in this particular study, because we’re looking for such a huge effect, we’re actually looking for an ALS reversal. We don’t have to have any narrow inclusion-exclusion criteria, we don’t need a lot of patients, and we actually don’t need a placebo group. We can use a historical control group to figure out if anybody in the study got better. The downside of doing a study like this is if there’s a small effect, we’ll miss it. We’re looking for the home-run effect in this study and if there’s no home-run effect, we’re going to move on to the next thing than an ALS reversal trial. That’s what this program is all about.
Caller: Thank you.
Seth: And thank you, Caller, for that question. Going on to our next caller, caller ending in 0899, you are on the air.
Caller: Thank you, Dr. Bedlack, sure appreciate all of your work. You’ve mentioned on this CReATe project, you seem to have just an amazing grasp on the possibilities of what could happen and what could be done in the whole ALS fight.
Are there other disease communities that you admire as far as how they’ve attacked a disease that you like to look at as a model of how the ALS community can come together?
Dr. Bedlack: Yeah, that’s a great question.
I do admire a lot of other groups that are out there that has made progress in their disease like for example, the folks working in HIV. I think the amount of collaboration in that field and the fact that there are people studying these very rare HIV phenotypes, like the elite controllers, and having some success figuring out what it is that allows those folks to beat HIV. I think that we need to pay attention to that and that’s part of why I’m so excited about this ALS Reversals project.
Caller: Thank you.
Seth: Thank you, Caller. Going right along, caller ending in 1243, you are on the air.
Caller: Hello. Thank you, Seth, for this great radio show and thank you, Dr. Bedlack, for all your hard work that you do.
Dr. Bedlack: My pleasure.
Caller: My question is I am vent-dependent but I can still speak and swallow. Would I be excluded from pretty much all of the clinical trials that are going on right now? Because I know there’s a shortage of people and I would be more than happy to participate.
Dr. Bedlack: Yup. So it’s important to take a step back and remember that this business about participating in research, there’s a lot of different kinds of research that are important. Clinical trials are only one type of research. So for example, we’ve got epidemiologic research, biomarker research, genetic research. All that research is going to be really important in helping us eventually beat this disease and there’s no reason why you would be excluded from many of those kinds of studies like for example the National ALS Registry or some of the genetic studies that are going on.
When it comes to trials, traditionally, like I said before, we’re looking for such a small signal in such a noisy disease that we have to try to homogenize the patients as much as we can and that’s part of why we have such narrow entry criteria in trials. It won’t always be that way. Someday we’re going to be able to subdivide patients based upon a blood test hopefully or an imaging study to figure out what subset of ALS they have and we’ll be able to have a lot less noisy disease when we do that and therefore a lot wider inclusion-exclusion criteria.
But for right now, unfortunately there aren’t many trials that folks with very far advanced ALS who are on ventilators can be in and that’s another reason why I’m excited about studies like the ALS Reversals project where we’re looking for big signals and we can bring just about anybody in as a result.
Caller: Okay, all right. What website can I go to to find something that I can participate in?
Dr. Bedlack: I think the most comprehensive place to go for research opportunities is clinicaltrials.gov. The downside of that website is that its not the easiest to navigate but hopefully you’ll be able to get help maybe from your clinic that you go to and be able to type in ALS. Look for open studies and you can even put in a zip code to figure out how far you’re willing to drive to be in a research study and they’ll tell you what’s open and you can kind of look quickly through the inclusion-exclusion criteria and find out which ones you might qualify for.
Caller: All right. Well, thank you very much. Once again, thanks for all your hard work that you’re doing for us.
Dr. Bedlack: Well, thanks for listening today.
Caller: You bet. Thank you. Bye.
Seth: Thank you, Caller. Our next question came to us online. “How can one communicate with ALSUntangled other than through social media? Is there an email contact?”
Dr. Bedlack: Yes. So you can email me anytime. It’s firstname.lastname@example.org. And if you forget that, then you can also Google the Duke ALS Clinic and you can find my email on there.
Seth: Excellent. Thank you.
That brings us to the end of our caller queue. I did want to ask, Dr. Bedlack, if you have any closing thoughts you would like to share?
Dr. Bedlack: Yes. So a question that I get asked a lot is what’s the greatest opportunity for people to get more involved and I think there’s multiple parts to this. I think first of all, join every research study you can. Even if it’s not a trial, that doesn’t mean that’s not important. In fact, I would argue, based on kind of where we are in the history of ALS, studies that tell us more about what’s causing ALS and why people who get it keep getting worse are probably even more important than the trials because we need to understand this disease better before we have trials that are going to be curative.
I think you should try to become a research ambassador by signing up for one of our clinical research learning institutes and we’re going to have one of those in January that’s going to be virtual so people all over the world could potentially be research ambassadors without having to travel like you and Amy did, Seth, to Florida.
And then finally, I think if you’re one of the more than 50% people with ALS who are thinking about trying one of these alternative or off-label therapies, don’t be afraid to have a conversation with your doctor. And then maybe most important of all, if you do try it, make sure you sign up for a website like PatientsLikeMe and input your outcome measures so that the world knows what happened to you. Because I think that’s probably the most tragic of all the things I’ve seen in the past five years is that I know there are a lot of people who’ve tried these things and they never blogged about them and they never put their data in any place. So whatever happened to them is unknown and that’s a shame. I think we need to learn something from every patient with ALS especially those that are out there trying things. We need to learn from that.
Seth: I completely agree. And for those of us who wish to donate to your research, how do we go about that?
Dr. Bedlack: So there are a couple of different ways, we don’t actually have a formal donation program for ALSUntangled. But if you donate it to the Duke ALS Clinic and wrote on your check, you wanted this to be for the ALSUntangled account, we would certainly create an account. Again, the purpose of that, the next sort of thing we’re trying to get enough money to do is to protect some time so that I might be able to do like a half-day a week of nothing but ALSUntangled so it’s not just the nights and weekends part-time project anymore. I think it’s gotten to be almost too big for that now. So hopefully we’ll be able to make that happen in 2015.
Seth: Excellent, thank you.
We sincerely appreciate your time both on the show and in looking for a cure for us in the community. We applaud your work and encourage you to keep going. Thank you.
Dr. Bedlack: We’ll do it, Seth. Thanks to you and Amy.
Seth: You’re welcome.
For our listeners, a full transcript of today’s show will be available in coming days on alscrowd.org. Thank you to Dr. Richard Bedlack for his time. Bye for now.