ALS Crowd Radio S2:E4 Dr. Richard Bedlack,MD, PhD, MS Duke University: ALS Reversals

Dr. Richard Bedlack, MD, PhD, MS
Duke University
Interview Date: May 4, 2016

S2:E4 Dr. Richard Bedlack defines an ALS Reversal, in which a patient with a confirmed diagnosis of ALS regains motor function.  He describes his search for these cases, which has revealed 23 to date.  He started the ALS Reversals Program which includes two parts: 1)Replication of ALS Reversals (ROAR) and 2)Study of ALS Reversals (STAR).  Dr. Bedlack’s first replication pilot study is underway with Lunasin and is different from other clinical trials because it can include most ALS diagnosees. He describes this method of studying ALS from the patient side, rather than from the lab.  He hopes to collect enough ALS reversals to mine the data and find similarities, an approach that brought success in HIV treatment.  Dr. Bedlack believes there are many research breakthroughs happening; that this is the most exciting year for ALS in his 16 years in the field.   

ALS Crowd Radio Episode with Dr. Bedlack:

Full transcript:

Seth: Hello and welcome to ALS Crowd Radio Season 2 Episode 4. I am your host Seth Christensen here with my co-host Lori Wangsgard.

Lori: We are excited to interview Dr. Bedlack today. If you have a question, please call in at 516-590-0362 and press 1 to indicate that you have a question. Now I would like to introduce our guest.

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 an MD and PhD in Neuroscience at UConn. Finally, he came to Duke where he completed his Medicine Internship, Neurology Residency, Neuromuscular Fellowship, and Masters in Clinical Research Science. He is currently a tenured Associate Professor of Medicine/Neurology at Duke, Director of the Duke ALS Clinic, and Chief of Neurology at the Durham Veterans Affairs Medical Center. 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 Patient Advocate of the Year and the Rasmussen ALS Patient Advocate of the Year. He has received ALS research grants, participated in ALS clinical trials, published more than 60 ALS articles and recently edited a new book called ALS: A Patient Care Guide for Clinicians. He is the outgoing Chairman of the North American ALS Research Group and leader of 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: Dr. Bedlack. Welcome to this show.

Dr. Bedlack: Well thanks for having me back, Seth.

Seth: We’re thrilled to have you. I believe we had you on the last about a year-and-a-half ago, to talk about your work with ALSUntangled. How is that work going?

Dr. Bedlack: I think it’s going great. The program is getting bigger. I think it’s getting better. Since the last time that I was on, we have refined the way that we actually do our reviews. So we have always had a way to gather information sort of a standard operating protocol by which we gathered our information for our reviews but now we have got something called the table of evidence. So it’s a structure that we try to use for all of our reviews. We try to make sure that everything we look at, we grade it according to five categories.

We grade it according to its mechanism of action, in other words this particular treatment is it actually do anything that might be relevant in ALS. We grade it in terms of its preclinical data. So was this thing ever given to any sort of model of ALS either a test tube model or animl model? We grade it in terms of its effect on individual patients. Those are kind of like case reports that we might find on the internet like in chat rooms or that maybe one of us has seen in our clinic. We grade it in terms of any clinical trials that were done. Unfortunately, many of the things that we look at don’t have any clinical trials. And then finally we grade each one of these things according to their risks. And for each of these five categories, we assigned a letter grade ranging from A to F. A is the best, F is the worst and there is very specific things you have to achieve to get the next best grade in each of those categories. We have tried to make this process very objective.

Seth: Wonderful. For those of our listeners new to ALSUntangled, what is the program in a nutshell?

Dr. Bedlack: Yeah. So back in the beginning of my career, it became obvious to me that many patients with ALS were going home from clinic and going on the internet. The internet is just full of things that are advertised to potentially be useful in the treatment of ALS and you could understand why patients with ALS would do that. I mean here I am in my clinic trying to provide them with as many options as I can but I still don’t have the bullet that stops or reverses ALS. Folks wants to believe that maybe there is something better out there.  They that go on the internet and there are a lot of websites that make extraordinary claims about treatments for ALS and unfortunately there is no internet police to go around and try to validate these claims.

You could open up a stem cell clinic in Siberia and say that you have treated a thousand people with ALS with your stem cell and that every single person got better and you never had a single side effect. Who can actually hold you to do that? There is nobody that’s in charge of doing that. So we created this program to try to help patients and families make more sense of all these different alternative options. There are three parts to it.

First, how do we get our information and that is that patients can send it to us in a variety of ways. If you want to hear about a particular alternative therapy that you saw on the internet, the first thing I would suggest is go on our website, see if it’s something that we already reviewed or something that’s on our list of open reviews, something that we have got scheduled. If it’s on the list of open reviews, click the button that says vote and it will move up the list and that’s how we prioritize. We try to get the reviews that have the most votes next.

Then second, how we do our reviews and we talked a little bit about that with the table of evidence. And then the third part of it is how do we get the information back to patients and families. So we write articles, scientific articles which have a hundred authors. There are a hundred people like me around the world that are part of this program and this article gets circulated amongst all 100 authors and everyone kind of weighs in and we go around it around with different drafts. When we finally have it to a point where we can all agree that it’s publishable, we send it into the ALS Journal and they do a final review, their editor reviews it. And if they have no more comments then they publish it and these articles are all published free open access. So patients and families can read any of them for free. They don’t have to pay anything.

Seth: Wonderful. We are out on ALSuntangled.com right now. We see that many of the topics covered in recent episodes are trending as open reviews with your team right now. We’re very excited and encourage our listeners to go to ALSuntangled.com and read more about many of the topics we have all heard about. Thank you for that explanation.

Dr. Bedlack: Sure thing.

Seth: We’re thrilled to talk a little bit more about a bit of a different topic, but Im sure related.  You are a bit of a celebrity in ALS reserach right now and one of the topics that you speak on is ALS Reversals.   Can you explain to us what a reversal is?

Dr. Bedlack: Sure. Well I’ll tell you how I got interested in this. A few years back around 2010, I was doing ALSUntangled review on an energy healer by the name of Dean Craft. And I was going through his website which is really just a treasure trove of letters from people all over the world to claim that they saw this man do something that should not be physically possible like move a pendulum that was underneath a glass jar using only his mind. Of course, it’s interesting but there is no way to really validate any of these letters. But on that website, there was a video about a patient who was said to have been diagnosed with ALS at one of America’s top medical centers was said to have progressed to the point where she was completely paralyzed and near death, the video I think verbatim says her family was picking out her outfit to be buried in.

Then she went to Dean Craft and two years later she is back to normal. She can run. She can throw snowballs with her grandchildren. When I saw that, I didn’t know what to think. I have never seen anything like that before. My first thought was let me see if I can find this person, see if this person is even real and sure enough with social networking I was able to find some friends of hers who connected me to her. I spoke to her on the phone and she was nice enough to not only corroborate the story but also to send me a whole box of her medical records.  

I’ll never forget going through those records; as I got about halfway through and I had the goosebumps. I turned to my wife and I said, “You know how people already think I’m kind of crazy. They’re going to be really be amazed when I stand up at the next meeting and say I think I might have found the cure for ALS, energy healing. Because I’m absolutely sure reading through those records that she had ALS. I mean she had all the right story, all the right exams, all the right EMGs, all the testing that should have been to rule out mimickers. I’m sure she progressed to where she was quadriplegic and unfortunately near the end of her life. And now I’m sure that she is, if not 100% normal, pretty close.  And so I didn’t know what to think.

My first thought was, well it must have been this treatment, but it’s so surprising. Then the more I thought about it and searched the literature and talked to colleagues, there are other people that are out there that have had stories like this that did completely different things or in some cases didn’t really do anything at all. She is not the only ALS reversal and it led me to start thinking you know there is probably different possibilities for these ALS reversals. One possibility is that maybe there is another ALS mimicker out there that none of us knows about something very rare that we don’t usually test for. Another possibility is maybe some patients are genetically resistant to ALS. In other words, their bodies can figure out a way around it. And that may sound crazy but it turns out there is a president for that.

In the HIV field, there have long been a group of people called elite controllers. They get infected with the HIV virus, can measure it in their blood but they never get sick. They don’t take any medicine. For years people kind of shrugged their shoulders and didn’t know what to make of those folks and then somebody put them all in the same database and did some genetic testing and found that many of them have the same genetic abnormality. And when they figured out what that gene does, it codes for a protein. It’s in the surface of all of our cells that HIV needs to get in. Because of their genetic abnormality, that protein looks different and HIV cannot use it to get it to their cells.

We learned something very important about the biology of HIV by studying this very odd subgroup and now a company Pfizer has developed a drug which blocks that pathway that works for everybody with HIV. So maybe if I could find what makes some people resistant to ALS, maybe I could learn something about the disease that I could give to other folks.  Then the last possibility Seth is that maybe some of these unusual treatments really do work. I can’t discount that. So I started this whole program called ALS Reversals to try to work my way through these three different hypotheses and there are really two arms to this.

There is something called the Star Program, the STudy of ALS Reversals. There I’m trying to gather as many of these patients as I can.  If I can get as much clinical information on them into the same database to see what they might have in common with each other that might look different from other people.  Say for example, they all have a disease like Myasthenia Gravis, that would be very interesting. I don’t know yet because I don’t have them all in the database. I’m also trying to get blood on them to see if I could do some genetic testing like they did in the HIV field.

Then the second arm in my program is called ROAR, Replication Of ALS Reversals.  In that particular program, I am doing small pilot trials of the exact same treatments that some of these patients tried when they had their reversals. You probably have heard the story about Lunasin and the associated ALS Reversal and that’s my first ROAR pilot trial, the Lunasin trial.

Seth: Well for those new to Dr. Bedlack’s work please go to ALSreversals.com and read more.  Dr. Bedlack how many ALS Reversals are you looking at? Are these five people globally or is this a larger number?

Dr. Bedlack: Well I have 23 confirmed ALS Reversals now where I have enough medical information to be reasonably sure that the diagnosis is correct and that the reversal is very obvious. At 23, it’s not really enough probably to do the kind of genetic testing that I’m interested in doing. I’m going to have to find more. So part of what I’m trying to do right now is survey my colleagues around the world so that they’ll send me their cases of ALS Reversals. I’m trying to find more online and I do have at least six more that I’m looking at that I found on various websites but I don’t have records on. I’m trying to find those people. I’m trying to communicate with them to see if they’ll send me their records so I can try to confirm what it is that they are saying about themselves.

And then I’m also trying to work on a definition of ALS Reversal so that it doesn’t have to be so nebulous. Right now my definition is well, if they obviously got a lot of motor function back, that’s not supposed to happen so that’s an ALS Reversal. But it would be nice to be able to say something like, you know, if their course was two standard deviations better than it should have been by our predictive models or if they regained four points on the ALS functional rating scale after 12 months then we’ll call that a reversal. I still haven’t got that definition yet that I’m really excited about that the scientific community agrees as a good definition. But right now, my definition is you have to have a confirmed diagnosis of ALS and it has to be really obvious that you have regained motor function.

Seth: Excellent and to clarify, those are 23 currently living people?

Dr. Bedlack: Good question. So a couple of these people I don’t know if they’re still alive. Some of these folks I found back in 2010 and I have not been back in communication with them since. Once I get this Star Program up and running which I’m supposed to get a helper this fall and once I get that helper, we’ll be able to actually get this database built and get some surveys out there and really ramp this up, give it the amount of time that it really deserves. Right now, this is kind of a nights and weekends type of project. But once I get a helper, we’ll have somebody who’s devoted at least part time to really helping me grind through this.

I have been focusing more on the other arm, the ROAR arm because I know that there are so many folks who want to try things.  I have spent really the last year of nights of weekends trying to get that Lunasin trial off the ground. It actually took me quite a bit longer than I expected.  There were a lot more unexpected delays getting that off the ground but it’s finally up and running. We have been up for about a month and we have enrolled our first 16 patients in that now.

Seth: Excellent, I will invite Lori now to tell listeners how to ask a question.

Lori: Thank you. We have callers from around the nation. If you are already listening by phone, you can press one to indicate you have a question. If you are listening on computer, the best way is to dial in to the phone 516-590-0362 and then press 1 to indicate you have a question. You will be on hold and can still hear the show on the phone.

Seth: Excellent. Thank you, Lori. Though this is quite a night and weekend project, Dr. Bedlack tell us a little about your end vision for this project.  Will one assistant be enough or do you envision this being a larger program?

Dr. Bedlack: Well you know, Seth. I think it depends on how many of these reversals I can find. I’m hoping I could find a hundred reversals by some definition that other scientist will accept  as valid because I think if I can find a hundred, then I have got a big enough number to actually do some of that fancy genetic testing that I was talking about, something that’s called whole genome sequencing. Twenty-three is a pretty small number. I mean if they all had the exact same genetic abnormality, I might get lucky. But you know how things go.

The chances are if I’m lucky, most of them like the elite controllers will have the same genetic abnormality but it may be a stretch to think that they all have the exact same problem or the exact same abnormal gene that’s actually turning out to make them resistant to ALS. But yeah, no I mean it’s — I would love to be able to really devote the majority my non-ALS clinic time to this project. I am incredibly excited about it. I think it’s something totally different. As I said, I think there is a blue print in another field, HIV where this type of approach was very successful. I don’t think it’s completely crazy to think that this might lead us somewhere.

Seth: If it is completely crazy, we applaud this lunacy.

Dr. Bedlack: Well thanks.

Seth: It’s a creative approach and we are hungry for it. Just for our education, can you share any more cases studies that you’re working on besides the Dean Craft example?

Dr. Bedlack: Yeah. So I can tell you about some other reversals that I know about that are amongst the 23 that I have collected. So there is an ALS Reversal that was associated with the drug Aims Pro, A-I-M-S P-R-O, which is also known as hyper-immune goat serum. There is an ALS Reversal, a famous rabbi that’s been in the news that was just associated with the Brainstorm cell trial. There is an ALS Reversal associated with the Neural Stem, stem cell trial. There is an ALS Reversal associated with Lunasin which is the one that I have based my whole first trial around. There is an ALS Reversal associated with Protandim. There is an ALS Reversal associated with the drug NP001.

And the latest ALS Reversal that I came in contact with is detailed in the most recent ALSUntangled article on hyperbaric oxygen and this is a man who has put himself out online, so there is no problem revealing his name. His name is Kim Cherry and he’s got a website called ALS Winners. He really does appear to have ALS from his medical records and he really does appear to be getting better. The complicated thing about Mr. Cherry is that he is doing a lot more than just hyperbaric oxygen. He’s doing a very complicated cocktail including intravenous ozone, a number of nutritional supplements, dietary changes and attitude changes. And it would be a challenge to try to do a trial of exactly what he has done to himself. It’s been a challenge even to do this Lunasin trial because Lunasin is actually three products in order to do exactly what the ALS Reversal did on its three different products.

That is part of why this thing took so long to get off the ground. You know imagine trying to do a trial that had ten different major changes including things like hyperbaric oxygen and intravenous ozone and special diets and things like that, it would be difficult to get started, never mind difficult to actually measure the compliance of. There is a lot of interesting things out there that people are doing but those are the ones so far that I have seen at least one ALS Reversal with.

Seth: Thank you. At least by my count, four of those happened during the course of a regular phase two or phase three trial. I’m curious as a researcher, can you talk about why those reversals would not have approved the use of those drugs further?

Dr. Bedlack: Well I think, I wasn’t in charge of any of those trials but I think the reason that there wasn’t a lot more excitement about those particular cases was that it was just one case. I mean I think if you had three or five reversals, then I think you really could make an argument that there is definitely a subset of people that seems to be benefitting from this therapy. But when it’s just one, you have to wonder like go back to my different hypothesis. I mean was this person, did it just so happen to occur during this particular treatment? Might it have occurred anyway if the person wasn’t even in the trial? Again you would hope that if there was one of these things out there that is really causing ALS Reversals that we could find something that had two or three reversal and not just one.

I don’t know which of the three hypothesis is right but I think the fact that none of these treatments have more than a single reversal, it makes me think that one of the other two hypotheses, either the mimicker hypothesis or the genetic resistance hypothesis, is more likely to be accurate than the treatment hypothesis. But we are going to keep all of our avenues open and we’re going to explore them all.

Seth: Excellent. I will ask Lori to invite more questions.

Lori: Thank you. Again the phone number is 516-590-0362 and press 1 to indicate you have a question.

Seth: Thank you. Dr. Bedlack, how has this side project been reacted to in your ALS research circles?

Dr. Bedlack: You know I’m pleased to say that the people that are working on ALS around the world are very open minded and very collegial.  The first time I really kind of mentioned this in a public forum at a research meeting was this past December at the international symposium in Orlando.  It was met with a lot of very positive responses and a lot of good constructive criticism including this idea that I need to try to think more about how I define these reversals because at that time I was thinking about defining them as this four-point improvement in the ALS FRS score lasting a year and that was — I mean I don’t think that was met with a tremendous amount of enthusiasm. So I appreciate that people are open-minded enough to consider this as a legitimate way to look for treatments and also care enough to be able to give me some good constructive feedback to keep going back to the drawing board and making this better.

Seth: Can you share with us why that definition is so important? Isn’t any improvement good enough?

Dr. Bedlack: Well, Seth I a published this paper last year; this is what I was presenting at the meeting.  It shows that the natural history of ALS is not always a straight line in people. It turns out that it’s not that uncommon for people to have what’s called a plateau where they might go several months without getting any worse. And it’s even not that uncommon for people to have a small ALS Reversal lasting a short period of time like for example you know, a one or two-point improvement that lasted a few months. That’s a surprise to people because I think a lot of folks have this idea that patients with ALS they’re just going to keep getting worse. You know everyday they’ll be a little worse than they were the day before and that’s not necessarily true. The disease does bounce around a little bit.

We are trying to find something here that’s a little more robust than just that noise in the disease and that’s where it gets tricky. These 23 patients just telling their story is enough to make it obvious that something dramatic happened to them that is very, very unusual. But trying to pull patients out of a giant database, you’ve got to have some sort of way to define what you’re looking for to be able to pull it out of there. What I’m kind of shifting more toward is we have got these predictive algorithms, like this company called Origent has won the Prize for Life to be able to predict within a big database called ProAct, how patients with ALS are going to progress with very high accuracy. But it’s not 100% accurate.

And so one of my ideas for a definition is what if we changed the term from ALS Reversal to ALS Resistance? And we say, let’s look for people who do two standard deviations better than the model predicts they should have. That might be an easy way to pull out a large number of folks from a database and say now what is different about these people? What can we see? I mean were they older? Did it start in a different place? Were they on some different nutritional supplement that was captured in the original study that they participated in. So that’s kind of where I’m focusing my efforts now on the STAR part of the program is trying to figure out how to define this and just kind of playing around with different definitions and seeing what that does in ProAct in terms of numbers of people that it pulls out for me.

Seth: Excellent. For those new to the term ProAct, this is a Harvard generated database built of big data collected over the course of medical drug trials.  And it is currently, I believe, the largest single ALS database in existance. Thank you for that.  Does that definition, Dr. Bedlack, include those ALS patients who are living 15 and 20 years?

Dr. Bedlack: Yeah. That’s one thing I like about it Seth. I’m of course most interested in the people that got dramatically better but I don’t know if there is enough of them to give me the kind of information I need. So maybe if we could add to that mix, people that had really long plateaus.  Many of your listeners may know the story of Steven Hawking and I have seen the movie, the Theory of Everything. It seemed like you know for the first decade or so, he progressed pretty obviously and then it seemed like for the next four decades, if he progressed at all, it seemed like he was really slow. So he is one of those people that you would have built a predictive model and he would have beat it significantly. There is something different about people like that and maybe the term ALS Resistance is a better term than ALS Reversal in terms of getting the right numbers of people to do these kinds of studies that I’m envisioning.

Seth: Excellent. Thank you again. We will take an opportunity now to get a question from one of our listeners. Listener ending in 9832, you are on the air.

Caller: Hi, Dr. Bedlack.

Dr. Bedlack: Hello.

Caller: My question — just to continue with that conversation, ALS seems to be a big box that you get the symptoms, you get tested and then you’re kind of thrown in even though your progression for many patients are so different from each other. Do you feel like these are actually different diseases, someone who dies within six months or someone who can live six, seven, years or 14 years?

Dr. Bedlack: Yes, I do think that the term ALS is probably more than one different disease. The clear evidence for that is that we know 10% of patients with ALS actually have a bad gene that caused their disease and that 10% of patients, there is now more than 40 different genes that can cause what we call familial ALS.  Those are different genes. They cause different pathways to be abnormal and yet they all kind of lead to the same place in upper and lower motor neuron disease that’s disabling and life shortening. They all have different progression rates. So if we know familial ALS is heterogeneous, well then sporadic ALS probably is too. I mean there is probably more than one cause of sporadic ALS and there is probably more than one pathway that drives progressions in people with sporadic ALS.

What you are getting at is really sort of the difference between patients right from the start of the illness. I think that may be a separate question, but I think it’s an important one and I think biomarkers are what’s finally going to allow us to be able to tease that apart. So for the 10% of people of familial ALS, we have a biomarker. We know what sort of disease they have. We do genetic testing. We know that this person has C9 orf 72 ALS and that person has SOD1 ALS and the types of drugs that we try on those patients might be different. But maybe in people with sporadic ALS, a biomarker would be something like what Dr. Atassi at Mass General Hospital is working on with his PET Scan tracer that’s only picked up by activated microglia cells so that we can identify the subset of people who have that as the primary mechanism that’s driving their progression. Drugs that attach that mechanism, we would only test it in those people that have that mechanism active.

But I wonder though if it’s a separate question, there are clearly differences between people. What I’m interested in are the differences within people like why are there people who seemed to progress just like the average person with ALS for a while and then they either stop progressing or they are completely reverse and get better? You know that, I don’t know what that is. I mean that may be a different form of a disease or it could be like I say some host factor that makes them resistant to the same form of disease and lots of other people have or it could be one of the treatments that they tried that actually turned things around. I don’t know. I almost see that as a separate question but it’s a very important one.

Caller: I’m not familiar with your Lunasin trial. Could you expand on that and talk about the criteria to meet that trial? To be in that trial?

Dr. Bedlack: Yeah. So this trial is unusual for a lot of reasons. First of all, it’s unusual because of the way that we got the idea. Most of the time in ALS trials, our ideas come from things that we saw in a test tube or in cell cultures or in our animal models which are based on genetic mutations. As I said before, the idea for this trial came from a person who appeared to have sporadic ALS and did something and then got dramatically better. So that’s a model that we really haven’t used before in ALS.

Other things that are different about this, it’s very open. We’re allowing almost anyone with ALS to be in this. There are of course a few rules. I mean it is a one-year long study. Unfortunately if your doctor doesn’t think that you can survive a year, I can’t put you in the study because I need a year’s worth of data in order to get an answer. You also have to be able to use a computer and have internet access because we’re making patients full partners in this and we’re going to actually teach them how to measure things in themselves and how to enter their own data on a website. So the first thing that’s unusual is that it’s so wide open and part of why we can do that is with most trials we are looking for a tiny signal in a very noisy disease. If you are looking for 10% slowing in the rate of progression on the scale like the ALS function or rating scale, well you got to really try to homogenize your population as much as you can. We’re looking for a gigantic signal. We’re looking to see if anyone gets better on this. Do they actually regain motor functions over the course of a year? So we don’t have to worry so much about the noise.

We are also not going to have a placebo group. We definitely appreciate the need for placebo groups in phase three trials and especially when you are looking for small effects. But again this is a pilot study and we’re looking for a huge effect. So if at the end of a year, if five out of 50 patients have an ALS reversal, I’m not sure that anyone is going to say, well gee, you didn’t use a placebo. How could that be a placebo effect if people are actually reversing their ALS?

We’re also going to have very few visits required. Many trials are too burdensome for patients. Patients sometimes in my clinic look at trials and say, “Man, I don’t know if I can keep making monthly visits for an entire year and spend all that time in your clinic getting all those measurements.” So in this trial, we only have three visits, the screening visit, the one month visit and then the one-year visit. And everything in between is going to be patients on their own home computer entering their own data.  If they are not entering it, we get a little prompt from the system and we call them to try to find out what’s going on and they’re having trouble with their computer, have they just given up on the study? What is it?

And then finally, because we’re using Patients Like Me and because that’s publicly available information, anybody anywhere in the world can take a live look at our study. A lot of times patients tell me, “Gee, this study that you want to do, it’s a yearlong and you’re telling me it’s going to take a year to enroll. That means I won’t have any information about whether this drug worked or not for two years? That’s pretty frustrating.” Well, you can look at our data anytime you want. You can just go and Patients Like Me and type in Duke Lunasin study and you could see what’s happening to the people in our study, see if anyone is having an ALS reversal.

Caller: Wow. That sounds incredible. We’ll watch closely. Thank you for your time.

Dr. Bedlack: You bet. Thanks for your questions.

Seth: Thank you, caller, for the great question. Dr. Bedlack, before we wrap up, our callers are always curious about how they can personally support your research. How can we do that?

Dr. Bedlack: Well as far as the ALSUntangled program, we’re fortunate now to have two great sponsors, the ALS Association and the Motor Neuron Disease Association. With their help, I think we have all the financial resources we need but we definitely need those ideas to keep coming in. If you get ideas about things that we haven’t thought about yet, be sure to send those in. You can see on our website all the different ways you can get those ideas to me. Be sure to go on there and vote under the open review so that we know which of the more than 200 things that people have asked us about, do the most folks care about? And be sure to download and read our reviews because that’s one of our measurements that we used to determine if the program is actually useful. You know how many people are actually reading our reviews.

And then when it comes to ALS Reversals, this is right now an entirely patient funded project. We’re blessed to have a family, the Larry Vance Hughes ALS Foundation that is the primary sponsor of that program.  As the program grows, we probably will need some additional help there and certainly if we get some interesting pilot data, we’ll be able to apply for grants like to the ALS association and the NIH. And the other thing is if you’re out there and you hear about ALS Reversals please let people know that I’m interested.

One thing that’s been amazing to me is a lot of these folks are — they are sort of anti-doctor now. Some of these folks that I think might have ALS reversals that I haven’t been able to confirm yet, what I hear through the grape vine is that they are not interested in talking to doctors or scientists anymore, because I guess in the past, they were just kind of rebuffed. I do still hear that sometimes patients — their ideas are not taken seriously.  But I am genuinely interested in these folks and I’m coming at this with a totally open mind. I just want to hear their story and ideally get their records and see if I can confirm what happened to them because I do think there could be something important if we can get all these patients together. Those are some ideas that I have Seth along those lines.

Seth: Thank you. One final question, but do want our callers to have every opportunity, Lori?

Lori: The phone number is 516-590-0362 and press 1 to ask a question. We’re going to take our next question at this time from caller ending in 3662. Go ahead, you’re on the air with Dr. Bedlack.

Caller: Hi Dr. Bedlack. I was just wondering if you had any experience or opinion on this new Japanese approved drug called Radicut.

Dr. Bedlack: Yeah. So it’s also known as Edaravone. It’s a free radical scavenger and it’s an interesting history. So you may know that there were some preliminary studies on the drug in ALS that didn’t show any benefit and then they kind of went back and tried to pull subgroups out of those preliminary studies and see if there was a subgroup that might have benefited. After some manipulation of the data you are able to find a sub group and then they designed another study just of that subgroup, that’s called enrichment. And it’s an interesting way to do things. The problem is knowing whether the results then generalize to everybody else with ALS.

In my opinion I think because this is such an unusual paradigm, the results of that study really do need to be replicated. Hopefully somebody in United States is going to take the lead on that. I think they are. Unfortunately, it’s not the cure for ALS but there is a suggestion that it could slow it down. I definitely think it’s something that needs that needs to be studied further, be replicated. But in my opinion, I don’t think right now that the data is strong enough to say that everybody with ALS should take that. I think that there are still a lot of questions that I have about it than I’d like to see it replicated in a more traditional study.

Caller: Great. Thank you. I can’t wait to pour through the website and see all the other information on there.  

Dr. Bedlack: Well, I hope you like it.

Caller: I appreciate your work.

Dr. Bedlack: Sure thing. Thanks for your call.

Seth: Thank you, caller. Now to wrap up Dr. Bedlack, we have talked a lot about your specific focus but stepping back and looking at ALS as a community and as a larger problem, is there a great single opportunity for ALS families to contribute and get involved? Or should we simply focus researcher by researcher?

Dr. Bedlack: No. I mean I think it would be awesome if everybody with ALS tried to get involved in a study. So sometimes people say well I can’t find a study that I can be. Well there are some studies that everybody with ALS can be in for example the National ALS Registry and there is a group called Create, C-R-E-A-T-E. If people want to know what that’s about, just Google the word Create and then the words Rare Disease Clinical Research Network. It’s a national institute to help sponsor a group that is very interested in trying to do a whole genome sequencing in as many people with ALS and other motor neuron diseases as possible and try to tease out why do they look different?

And it goes back to that other caller’s question about “Can we identify ALS subtypes?” That would be so helpful. And then there are clinical trials. I mean there is more clinical trials going on now that I have ever seen in the history of ALS and some of these are just incredibly exciting. You probably saw some of these papers that have me with a big smile on my face. I mean one of them is a paper from a doctor at John Hopkins that was trying to identify the cause of sporadic ALS.  He was looking at something called Human Endogenous Retro Virus- K. Did you ever talk about that on your show?

Seth: On an upcoming episode, we will cover that. But no, we have not yet.

Dr. Bedlack: Well I don’t want to steal anyone’s thunder but it’s a very preliminary finding but it could turn out to be the most important paper in the history of ALS if this can be replicated, because it might have told us what the cause of at least some sporadic ALS is. And it might have identified a way to actually stop that form of sporadic ALS. Stay tuned on that. Then I’m incredibly excited about some of the things that I see in terms of biomarkers. I personally think that once we have some biomarkers, the field is going to really explode because then we’ll be able to subtype people and we’ll be able to pull out folks that are much more likely to respond to a particular drug that attacks a particular mechanism. So yeah, I have been in ALS for 16 years Seth, and I think this is the most exciting — this particular year that we’re having right now is the most exciting that I have ever seen.

Seth: Given that this listener base is not very good at being a patient or staying tuned, can you speak a little bit more about that finding and that paper?

Dr. Bedlack: Yeah, sure. So again we have struggled to fix sporadic ALS in my opinion, in large part because we don’t know the cause of sporadic ALS. It’s hard to fix something when you don’t why it’s happening in the first place. A clue that Mother Nature gave us 20 years ago was that there were a bunch of young men who were coming forward with what looked like ALS but were also HIV positive. And in those patients, when they were put on what was at that time the new cocktail therapy for HIV, not only did their HIV virus titers drop way down but their ALS like disease went away.

Everyone got real interested and said wow, could there be a retrovirus, which is what HIV is, that actually causes sporadic ALS? They started looking and looking for retroviruses in patients with sporadic ALS but what everybody was looking for was called an exogenous retrovirus, a retrovirus like HIV that comes from outside of us.

Unbeknownst to me, we actually all have retroviruses inside of us. I did not know this until I read this paper by this group from Hopkins. Our ancestors all got exposed to retroviruses and they either died or they incorporated those retroviruses into their DNA and they became what is referred to ask junk DNA. And no one has thought anything of it. They just thought it was just kind of sitting there not doing anything. This guy at Hopkins said “I wonder if one of these endogenous retroviruses could become reactivated to cause sporadic ALS?” And so, it is a very small study, but in 10 out of 10 people with sporadic ALS, there was evidence of reactivation of a retrovirus called the HERV-K and in nobody that they looked at without sporadic ALS was this retrovirus active.

When they took that retrovirus and they put it on motor neuron in a dish, the motor neurons died. When they gave that retrovirus to animals, the animals developed what looked like ALS. And so, this could be huge. It needs to be replicated in a much bigger sample but they are already in the process of doing that at John Hopkins and furthermore, when they find now people with sporadic ALS who have the activation of this retrovirus, they are starting anti-viral therapy on them, an HIV-like cocktail in them. So I think this is an awesome study to keep our eyes on. I’m incredibly excited about it.

Seth: We are too.  Dr. Avindra Nath will be on our show May 17th to talk more. Thank you for that.

Dr. Bedlack: Yeah, that’s going to be great. He’s a brilliant guy.  You’ll really like him.  

Seth: Thank you. Dr. Bedlack, we are incredibly grateful for your work in making time today.

Dr. Bedlack: It’s my pleasure, Seth.

Seth: Well we look forward to hearing more about your breakthoughs. Lori, can you talk a little about our next episode?

Lori: Our next show for ALS Crowd Radio will air on Monday 9th at 4:30 PM Eastern Time. It will be live from Washington DC at the National ALS Advocacy Day and Public Policy conference. We will interview both Barbara J. Newhouse, President and CEO of the ALS Association and Dr. Lucie Bruijn, Chief scientist for ALSA.

Seth: For now again thank you to Dr. Richard Bedlack for his nights and weekends and days. We’re grateful to have you on the team Rick.  

Dr. Bedlack: Well thank you so much, Seth.

Seth: All right, until next time.

Dr. Bedlack: Thank you.

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