• ALS Crowd Radio Episodes
    • Jul 04, 2014

    ALS Crowd Episode 1: Dr. Merit Cudkowicz on the state of ALS research today

Dr. Merit Cudkowicz, MD
Massachusetts General Hospital
Interview Date: June 26, 2014



Dr. Cudkowicz, MD of Massachusetts General Hospital and top ALS researcher, gives an overarching view of the state of ALS discoveries. She describes what ALS is and how its biggest challenge is its variation in each patient (heterogeneity).  She describes very exciting new approaches. One approach is a surgical approach using fetal stem cells by Neuralstem to grow new stem cells, which is being studied at the safety/dosage stage. She describes an approach using a patient’s own stem cells by a company called Brainstorm where the stem cells are removed, treated and returned to the patient. This approach is now in clinical trials in Israel and the US. She shares a Phase III trial by GSK that uses an antibody to affect a protein that stops neurons from growing. She explains another approach that uses skin cells to make motor neurons used in combination with an existing drug now used for seizures called Retigabire. She also explains a drug by Cytokentics that helps affect muscle strength. She notes that there is now greater interest in the scientific community to study ALS and is very hopeful about new discoveries. She shares how patients can learn about ALS clinical trials. She notes that the two most important hurdles to overcome in ALS research are to gather and study a large enough patient population’s biomarkers and then to acquire necessary funding to continue research projects that can move the field forward. 

The live ALS Crowd Radio podcast with Dr. Cudkowicz

Online Health Radio at Blog Talk Radio with ALS Crowd Radio on BlogTalkRadio

Full Transcript

Seth: Welcome to the inaugural show for ALS Crowd Radio. I’m your host, Seth Christensen, and we are thrilled to be here with you today.

A little first about the ALS Crowd mission: ALS Crowd is a brand new, not-for-profit organization, a division of the Crowd Care Foundation dedicated to connecting ALS patients and researchers to eventually develop a cure.

I as an ALS patient, was diagnosed four years ago. At the time of my diagnosis it was explained to me that ALS is a diagnosis that only comes through a process of elimination. There is no definitive biomarker or bloodtest to diagnose one with this syndrome and we today will explore this topic further.

You can follow us on alscrowd.org as well as our Facebook and Twitter page. At the end of today’s show, we will have time for Q&A with a number of callers. The call in for this online is 516-590-0362.

This time I would like introduce my wife and co-host.

Amy: Hi. My name is Amy Christensen. I am here to welcome our guest today. Her name is Dr. Dr. Merit Cudkowicz. She is the Chief of Neurology Service, Director of the Amyotrophic Lateral Sclerosis Clinic and Co-Director of the Neuromuscular Division at Massachusetts General Hospital. She is the Julianne Dorn Professor of Neurology at Massachusetts General at Harvard Medical School. Dr. Cudkowicz completed medical training at Harvard Medical School and was a resident in Neurology at MGH. She obtained her master’s degree in Clinical Epidemiology from the Harvard School of Public Health.

Dr. Cudkowicz’s research and clinical activities are dedicated to the study and treatment of patients with neurodegenerative disorders, in particular, amyotrophic lateral sclerosis (ALS). She directs the MGH ALS clinic and the Neurology Clinical Trials Unit. She is one of the founders and co-directors of NEALS, Northeast ALS Consortium, a group of 92 clinical sites in the United States and Canada dedicated to performing collaborative academic led clinical trials in ALS. In conjunction with the NEALS consortium, she planned and completed 7 multi-center clinical trials in ALS and is currently leading three new trials in ALS.

Dr. Cudkowicz received the American Academy of Neurology 2009 Sheila Essay ALS award. Dr. Cudkowicz is on the Research Council of the American Academy of Neurology and the medical advisory boards for the Muscular Dystrophy Association.

Seth: Now with that, we would like to welcome Dr. Merit Cudkowicz to the call. Dr. Cudkowicz, are you there?

Dr. Cudkowicz: Yes. Thank you, Seth and Amy, for having me for this inaugural radio show. I’m very excited to be here.

Seth: Well, you are an incredible part of the ALS community and a good friend of ours. So we’re thrilled to have you. Dr. Cudkowicz, I thought we would start off this inaugural show by somewhat defining ALS in as far as we can. If you could have a sort of a lay level, describe ALS to us and including what we know about its biology in relation to other disease categories.

Dr. Cudkowicz: Absolutely. ALS stands for amyotrophic lateral sclerosis. It’s also called here in the US, Lou Gehrig’s disease, and one might also hear it called in other countries a motor neuron disease. What it is is a disease that happens to people as they age, so something we call a neurodegenerative disorder. It affects these nerve cells called motor neurons. When those are affected, people develop symptoms such as muscle weakness or muscle twitching and cramps. It’s a serious disorder and it’s one that we really absolutely need to find cures and treatments for.

It’s rare. For example, in the United States at any one time, there might be about 35, 000 people who have ALS. Each year, about 5,000 to 6,000 new people are diagnosed with ALS in the United States. This is a worldwide illness. It affects all countries, all races, and ethnicities. It can affect all ages really. It tends to occur in the mid-50s on average but can hit people as young as 20, as old as 90. We really think it’s a syndrome, meaning that there are probably many different causes of ALS, though in the end, the illness is similar in that it’s really an illness of these nerve cells called the motor neurons and that we have in our brain and our spinal cord.

Seth: Excellent. Yeah, very much and that is a perfect introduction. I’m curious about what we do see globally. Are there any dissimilarities between the cases in the US and other countries? Do we have that information?

Dr. Cudkowicz: We do have information now on what ALS is like in many, many countries and particularly Europe and Canada. We’re really just starting to learn what it’s like in Asia and in some other places. In the big picture, it’s pretty similar in all these countries. There are a few spots in the world that are kind of hot spots where ALS is extremely common and a little different, for example, in the Key Islands in Japan and in also in Guam because sometimes it’s associated with other neuIrodegenerative diseases such as Parkinson’s disease or Alzheimer’s disease. Aside from those two palaces, it really does look clinically and biologically the same in all these countries.

Seth: Great. What are the variations in illness progress in different patients? Are young patients, for example, better off than their more advanced counterparts? Does age matter?

Dr. Cudkowicz: There’s huge variability between people with ALS. Some people who have very, very slow courses, fortunately, meaning that they might have the illness for 10, 20, 30 years, that’s about 10% of people with ALS. Then there’s the other extreme, another perhaps, 10%. They have a super rapid form–less than a year. Then there are really people who are everywhere in between. So that huge variation is really important for the field to try to understand, to try to figure out what causes that difference and how we can maybe make everybody a long, long super survivor of this illness.

It does vary with age. That was your question. So we know in general the younger someone is when they almost start so slower the illness and the converse, the older you are when it starts, the faster the course goes. But age is not really the primary driver of the huge variability that we see. We don’t actually yet know why again some people have this for 10, 20, 30 years and other people don’t, but there’s a lot of research going on right now to try to understand that.

Seth: Interesting. In addition to speed of illness progress, is there a difference in biologic onset? Are different people symptomatic in different ways?

Dr. Cudkowicz: Yes. So that’s a really good question. Yes, it does present differently between people. In about 80% of people, the illness will start in one of their limbs. It might start in the hand weakness, or the foot. But the other 20%, it starts in what we call the bulbar muscles. These are the muscles of speech, swallowing, breathing. The field is trying to also understand that variations of why it presents differently in different people with ALS.

Seth: Well, we are behind the field and there’s study of this. For our listeners’ sake, is there a leader in the collection of statistics? Is there a global body that attracts and disseminates information about ALS?

Dr. Cudkowicz: There are a couple of groups that are trying to really collect data from all patients with ALS. I want to say that I think this is really critical and a really important way to advance the field. These groups are working collaboratively. So I’ll just name a few of them. For example, there’s an ALS registry that is funded by the Department of Defense and run by the Center for Disease Control in Atlanta. Patients go to their website and enter data about themselves and there are questionnaires about risk factors, family history–really important sources of information. They also retrieve information from insurance companies, and all this pool of data is available for research. That’s one source.

The consortium that I direct called the Northeast ALS Consortium also has the policy that every research study we do whether it’s a trial or a biomarker study, that all that data from participants is shared with the research community. So we partnered with a couple of other foundations, the ALS Association, the Muscular Dystrophy Association, Prize4Life to gather all this large data set and make them openly available to researchers and there’s a project called POR-ACT.

Seth: Excellent. They’ll give sneak peak, maybe a spoiler at the end of the program, we do want to ask you how our listeners can get involved and how with these organizations and the others that we discussed between now and then. I thank you for that.

Changing gears, we would like now to talk about the state of ALS research today, where have we come from and what are we headed towards including the current trials and other hurdles that we still need to overcome. Perhaps, we could start off with theories that have been explored and proven wrong in the past. Could you speak to that point?

Dr. Cudkowicz: Globally, for ALS research, we’re way, way ahead of where the field was five or ten years ago. There’s an enormous number of people and companies and academics working on ALS, really globally. I think we’re in the time of a great hope. I’d also say that much of the work on ALS research really started in the ’90s. It hasn’t been that long that there have been the tools and the clues to really be able to study ALS. It’s still really in its infancy of trying to kind of figure it out.

For a time, there was a concern that maybe this was infectious and maybe a virus could cause it. I’d say that’s been largely proven wrong though it’s always hard to be 100%. The reason people thought it may be a virus is because polio is a motor neuron disease caused by a virus. So the thought was maybe there’s some other virus like that that’s causing this, and people looked hard for that and not been able to find at least any known virus.

I’d say that the other theories of ALS are still on the table. There have been a lot of them and they’re still active. I think that it’s important to keep them on the table because most likely ALS is not one disease. As I mentioned before that we really think that there’s many different ways that ALS can start whether it’s your immune system or something wrong with a gene in your body, or a protein problem, that it’s not one cause, one disease. For that reason, most of the theories are still kind of active in ALS.

Seth: I imagine that would be very complicated to deal with in a medical trial if you were trying to test a group of people and they may only have a different disease.

Dr. Cudkowicz: Absolutely. I think that’s one of our biggest challenges but not insurmountable. I think that it’s good to know what you’re up against and then try to figure it out so that you can do smarter trials and identify people who have maybe one particular biology, maybe that’s inflammation, and target drugs that target that biology, and use different drugs for different patients. Again, this is not unique to ALS. I mean I think most diseases come from many causes if you can think of just common diseases like high blood pressure. There are many different reasons people have high blood pressure and you’re treated differently depending on what the cause is. I think it’s the same for ALS. We’re going to get to the point where it’s different treatment for different patients.

Seth: Excellent. I am curious hearing you say that. What portion of the field is focusing on identifying a cause compared to the portion of the field that is attempting to treat. Is that a clear distinction?

Dr. Cudkowicz: I think it is a distinction. I’m not sure I know the proportions so I’d say that there’s a lot of effort on both ends. There’s a real belief that there’s a need to develop treatments for patients today that we know enough about the biology and not about the targets that we should be doing trials and therapeutic approaches now in people with ALS today. But while you do that, we really need to be supporting the basic science to understand the cause and the biology. Because the more we understand there, the better our treatments can be. So you really need both. I guess I’d say it’s probably about 50-50 at the moment.

Seth: Sure. How do you work on that plane while it’s in the air? I guess that’s the metaphor. Great. We would now like to move to probably the most exciting part of today’s show, which is discussing theories that are under consideration today and the trials designed to test those theories. Can you tell us about what keeps you up at night out of excitement?

Dr. Cudkowicz: Sure. I divide these theories into the genetic forms of the illness and the non-genetic forms. It can just take a minute to explain that.

So 90% of people with ALS do not have a family history or at least that we know of. So it’s what we call sporadic ALS. Then there are 10% people where the illness does run in their family. In those 10%, we know the genes in out 60% or 70% of those families. There have been huge advances in understanding the genetic causes of ALS. That is so important is because we think what we’ve learned from the genetic causes is going to be directly applicable to even the people without the family history. They can still help us understand the biology.

One of the most exciting things therapeutically is that with the whole gene revolution, we now have the tools to fix genetic mutations in people. There’s starting to be some trials just in the genetic forms of the illness and to fix the genetic mutation, and that excites everybody because it’s right at the cause of the illness and ideally really should work. We know it works in the lab and now it’s already starting to go into people.

Just for example, the two most common genetic causes of ALS are in the gene called SOD1 and another one, C9ORF72. There are companies and academics investigators working on ways to turn off those genes. One of them has already gone to patients in SOD1 families. I’d say that ALS is the pioneer there. This was the first time that type of approach was used for any neurological illness. Now, that approach is being used in many neurological illnesses. So that’s one area that really excites me and excites other people.

However, there are 90% of the other people with ALS who don’t have the genetic form and there’s still a lot of excitement there. One area that patients are surely excited about and I’m excited about is the use of stem cells in ALS and we’re early days here, and again the patients are really the pioneers here because its early days were stem cells in any neurological illness. There are two clinical trials going on now in the United States for people with ALS using stem cells.

Shall I talk about those now? Would that be helpful?

Seth: Yes, please. Go ahead.

Dr. Cudkowicz: One of them is with a company called Neuralstem. The idea here is to take stem cells that are from the spinal cord of a fetus and they’re grown to be nerve-like cells. They’re put in people right next to their motor neurons. So it’s a surgical approach. The idea is if you put healthy neurons or nerve-like cells right next to the entered motor neurons, can they create a healthy environment, secrete things that will make the motor neurons of the patient healthier? This has already been now done in two studies and about 30 patients have gone through this procedure. Again, this has never been done to anyone before, so the participants are really, really pioneers, and that’s moving forward into a bigger study now.

When we do these studies, the first thing you really have to figure out is safety and what’s the right dose. Dose in the stem cell trials is how any cells you’re putting in. These studies have really shown that so far that it looks like you can do this. This is safe and trying to figure out the right dose for people.

The other stem cell trial is with a company called Brainstorm. This uses people’s own stem cells. We all have stem cells in our body, in our bone marrow which is in our hips. They take those stem cells out and then they treat them so they have those secrete proteins that are good for your motor neurons that can help your motor neurons become healthier. They give those cells back to people in the fluid around the spinal cord and in the muscles. This is been done now in 24 people with ALS in Israel. They’re now bringing that study in the United States. It has officially started the three centers, Mass General, UMass, both in the Massachusetts and then Mayo Clinic in Minnesota.

I’m excited about both those. We don’t know if they’ll work. I mean we’re hopeful. There’s good science for them but I think it’s just the beginning of using stem cells as a way to help or kind of repair people’s motor neurons independent of what’s causing them to be injured in the first place.

Seth: To clarify what I think I just heard, we’re not looking at replacing damaged cells but we’re looking instead at causing an environment where they can follow the body’s natural tendency to heal.

Dr. Cudkowicz: Exactly. I think the idea of replacing a motor neuron is certainly something that people would like to do but the knowledge and the science isn’t quite there yet to do that. Certainly, there’s research in the lab to try to figure out how to do that but it’s still not ready for patient trials at this time.

Seth: Those are some of the most provocative or exciting studies. I assume there’s also more traditional pharmaceutical research going on?

Dr. Cudkowicz: Yes. Those are also really exciting. Even though started with the gene therapy approach and the stem cells because they’re really kind of the most novel in approach, it really could be that a small molecule or drug will be much more effective. We don’t know and it’s really important to keep developing those. There are, I’d say at the moment, probably about 14 clinical trials going on the in the world in ALS, in people with ALS. There’s a lot of promising therapies being developed. I’m happy to talk about a few of them if that would be of interest to the listeners.

Seth: Or maybe a one intermediate question. Do you know of those 14 trials, are they having any trouble recruiting patients, or is the subscription level higher than they can take?

Dr. Cudkowicz: I think there’s not one answer on that. There are some clinical trials that enroll very fast so that there are more people who want to be in it than can possibly be enrolled. But there are also other ones that are the opposite that even though the science is exciting, the drug is exciting that the enrollment takes longer than they hoped for. I think it has gotten much better in the last couple of years because I think the information is better that’s getting out to patients. I think patients and families know now much more about what’s going on. The trials are made known to people through webinars, through websites, or through their doctors in a much more proactive way, so that people have choices of whether they want to be part of it or not, and they have the information. That’s helped with enrollment.

Seth: Great. Thank you for that answer. Maybe we could go back and now talk about a few of those drug trials.

 Dr. Cudkowicz: Sure. When you develop drugs there’s what we call three phases of the development. The first one is when you’re first giving a new drug to people. It’s Phase I. They’re usually small, and you’re looking at safety in dosing. Then there’s a Phase II, which is maybe 100 people where you’re trying to look at longer-term safety and also is there a hint that it works, if things go in the right way. Is the drug doing what you hoped it should do? Then the last phase is Phase III. Those are larger studies maybe 500, 600 people. You’re really looking if it doesn’t work. If it works, then you go ask to get it on the market.

I want to talk about the one trial that’s in Phase III right now. That’s with a company called GSK, GlaxoSmithKline and the drug is what I call a NOGO-A body. The idea in this trial — the reason why I’m talking about this is we’ll have the results hopefully at the end of the year. It’s one that we’re going to have the results soonest from. The idea of this drug is to help repair motor neurons. So we all have in our bodies these proteins that inhibit the motor neurons from growing. One of them is called NOGO-A. This drug gets rid of the inhibitor. It allows your motor neurons to kind of sprout and regrow and repair themselves. That’s one approach that’s been taken to augment the body’s own ability to repair. It’s a study that’s going on internationally. We’re waiting for the results by the end of the year hopefully.

Seth: Okay, very exciting. Please continue.

Dr. Cudkowicz: Another one that we’re excited about, we’re going to be starting the next couple of months using the drug called Retigabine. This is also actually from the same company. Why I wanted to talk about it is because we’re always looking at ways that we can efficiently pick drugs that are going to be successful and how do we do that. So a new approach has been to take people’s skin cells. From their skin cells grow — you can actually make from people’s own skin cells; you can make motor neurons that kind of represent what their own motor neurons look like. It’s a very new technology, the persons figured it out got a Nobel Prize a couple of years ago. But it’s very important as a way to do an individual screening of whether the drug might work. We’re really hoping that this will be a way to screen drugs much faster for people with ALS.

When they did this they took skin cells from lots of people with ALS. They turned them into motor neurons and they studied them. What they found is, in people with ALS, these motor neurons were firing abnormally. It’s like something had turned them on. They were hyper excited. Then they went down to try to figure out why and they found that there’s a problem in something called a potassium channel. Then they looked, are there drugs out there in the market already that might be able to fix that problem. When they did that, they found one called Retigabine. This is a drug already on the market meaning that you can write a prescription for it for people with seizures.

But now, we want to use it for different reason–for ALS. A trial of this is going to start in people probably in the fall of this year to see what the right dose is and to look for safety and preliminary efficacy. The hope is that this should work. That’s the best thing if it works. Then the second thing that would come out of this is finding out if this is a good way to quickly screen for drugs. Again, getting back to this idea of more personalized medicine, if you can use people’s own skin and make the motor neurons and see if you can pick out what drugs might be helpful for them.

Seth: Extremely exciting. Are there other trials you care to mention at this time?

Dr. Cudkowicz: Sure. The other one I’d mention is with a company called Cytokinetics. This was a large study — what we call the Phase III — that was finished last April. This drug worked on your muscles directly. So one of the main symptoms in ALS is muscle weakness. This drug helped your muscles contract more efficiently to try to give them more strength. I would call it more of a symptomatic treatment. Can you give people more strength today so that they can do more things? The study was reported in April and it had somewhat mixed results but I think there’s some positive result in there.

When they looked at muscle strength, people on the drug actually did have higher strength as expected both in terms of their limb muscles as well as their breathing. But when they looked at overall function, they didn’t see a benefit. The study is now — it’s not yet going to market but the question is, should the field keep developing it given that that’s the only thing we’ve ever seen affects muscle strength in a positive way? The hope is that will continue so that we can figure out how to give it to people and get that benefit. I think we’re going to see another study of that coming up in the near future.

Seth: I’m curious whether these studies are primarily done by neurologists or if you have cross specialty interest as well?

Dr. Cudkowicz: The studies are primarily done by neurologists but there’s physiatrists who see people with ALS and do research. Physiatrists are rehabilitation doctors. The other healthcare professions that are very involved in the studies are, for example, like respiratory doctors or physical therapists, but most patients see neurologists and so most studies are run by neurologists.

Seth: Great. Where can our listeners find a list of these medical trials, their inclusion criteria, and progress?

Dr. Cudkowicz: There are a couple of options. I’ll tell you the easiest ones. Thanks to a donation from the ALS Association, we have a website that whose sole goal is to keep current information about clinical trials. That’s www.alsconsortium.org. That’s one place. Then also besides having the information of the trial, we have an email address that people can ask questions and also have a 1-800 number that people can call if they have questions about a particular study.

The other place is a government-run website called clinicaltrials.gov. Before any company or any investigator does a clinical trial, they’re required to post it on that government website. So it will always have any trial that’s about to start. Again, that’s www.clinicaltrials.gov. When someone’s on that website, you put in search terms so you’ll put in ALS, and it would list every study that’s going on in the world really. Mainly Europe, Canada, and the US use this website.

So those are the two that I tend to tell people that I see in the clinic. The other places one can go to are the ALS Association website,the Muscular Dystrophy Association, and the ALS Therapy Development Institute website. They also keep a list of ALS trials.

Seth: Excellent. Outside the governmental and institutional bodies, are there any private companies that are leading the way in the ALS community?

Dr. Cudkowicz: There are a lot of pharmaceutical companies interested in ALS which is great news because we need to work with them. They have knowledge in the drugs and we really try hard to get them interested and excited about doing something in ALS. Right now, there are very many of them and I won’t leave any of them out but I’d say Biogen Idec is leading and really committed to ALS, GSK, Pfizer, Roche. Many drug companies have ALS as a potential area where they want to develop treatment.

Seth: Excellent. Jumping to the funding question, do you have any idea or does anyone have an idea of money spent annually on research or dedicated to ALS research?

Dr. Cudkowicz: I’d say it’s not enough but I think that any disease group would say that. There’s data on this from NIH. I don’t know the latest numbers but I know at some point the government was funding in the order of $40 million a year. That sounds like a lot but it really, really isn’t. If you really want to tackle an illness you need a lot more resources than that.

Seth: I agree. Thank you for that. The last question in this category: is there a way to summarize the gravest challenges impeding research today?

Dr. Cudkowicz: I think the biggest biologic challenge is the disease heterogeneity; this difference between people. I think until we really understand the biology behind that, it will be hard to develop really effective treatments. Just as you mentioned before, if you have 1,000 people and who have ten different kind of biology going on in a trial and you’re only attacking one of them, you might miss a signal. I think the field has really recognized that now and is focused on trying to understand that biology. That’s the biggest, I think, biologic challenge.

I think the other big challenges what we’re talking about before is the funding. We need to be attracting the smartest, most innovative scientist into the field. You do that in two ways: One is they’re very excited about science. I think that’s there already. People are really hopeful and excited about ALS and feel it’s tractable and can be figured out. They need the resources. It’s very hard to get money from the government now. There have been huge cuts so people really depend much more on philanthropy or other type of sources of funding to get the work done.

Seth: On your first point about the complexity of heterogeneity, what is the research on biomarkers or ALS today? Are we making a progress on finding common characteristics?

Dr. Cudkowicz: I think we’re making progress on biomarkers but it could be much faster if done in a much bigger way. Right now, there are a lot of people looking at maybe 50 patients with ALS looking at their MRIs or spinal fluids or blood cells and lots of different groups kind of looking. In order to really figure this out, we need data from thousands of people. Everyone calls it the “big data” idea but it’s really true. If for us to really figure out ALS, we need to be engaged with the patients that when they come to our clinic, we’re collecting meaningful data and sharing it, and doing biomarkers in really thousands of people. There’s a lot of initiative to try to do this and it really is down to a matter of raising the funds for it.

Seth: All right. Please go ahead.

Dr. Cudkowicz: I could say that this is being done in Alzheimer’s and Parkinson’s disease and has led to huge, huge new insights into those two illnesses. In Alzheimer’s, the government paid for a big biomarker study, and Parkinson’s, the Michael J. Fox Foundation is funding a huge biomarker initiative. We need the same thing in ALS. I think it would really speed up our understanding of the illness tremendously.

Seth: Excellent. I really appreciate you focusing on what we can do. Before we go to get call ins, I’ll ask on more question. But do you want to invite anyone to call in? There is no wrong question and we would love to hear from you. The number to dial in is again, 516-590-0362. We will now ask the final, formal questions from Dr. Cudkowicz, and maybe you already covered part of this. What, in your view, is the greatest opportunity for our listeners who get involve and help?

Dr. Cudkowicz: I think the greatest opportunity would be if — for the people with ALS if you would participate in some of these biomarker studies, often it’s really donating a tube of blood. Sometimes it’s a little bit more. Spinal fluid or MRI study but being proactive about in a way letting us learn from you. I think that is the only way we’re going to really crack this illness. I know it’s a lot to ask from people but it’s really incredibly important.

Seth: Excellent. Thank you. With that, we will open the call line. If callers dial in and then press 1 on your keypad, you will be invited into the call. I believe we have a few people dialed in. We will start with Caller 1.

Amy: Hi, Caller 1, what’s your question today?

Caller:  Thanks for taking my call. If you look at the disease ALS and the downside associated with it, I wonder why the treatments –? Only one known drug out there in the marketplace and no known cures, why aren’t –? I don’t know maybe this is not a fair question, why aren’t people being more aggressive with the disease in terms of experimenting? I was talking with the head of Oncology at a local hospital today and he just said, “You know what’s the outcome is going to be, why not be more aggressive with it. It’s worth the downside of doing somebody’s more aggressive things in trying them out and sharing the results with others.” I understand there’s a safety protocol that needs to be invoked, but are there things out there that were not tried right now? Is there a way to just push the envelope a little more?

Seth: Great question.

Dr. Cudkowicz: That’s a great question. I do think that, certainly, in the last couple of years, the level of risk and aggression has gone up a lot. Just for example that stem cell trial where patients are going under a neurosurgical procedure to have stem cells put in their spinal cord as aggressive as you’re going to get, plus some of the gene therapy trials. So there’s been a huge shift in the last couple of years to really go out there and try to do things that has scientific rationale. Even if they would have a higher risk of maybe some of the drugs.

You’re absolutely right that the mindset in ALS is not the same as in cancer. Part of that is actually from the FDA. We do not have the same approach. The patients and doctors have gone and lobbied for some change there. I think that patients were heard and the hope is that there’ll be some change so that we can get therapists to patients quicker.

Caller: You’re saying that the lobbying has happened. I mean that’s something that we could do as caregivers and patients. Is there something else we can do in pushing that area or the lobbying already happened and just waiting for the outcomes of that lobby?

Dr. Cudkowicz: I think there’s always room for more lobbying but doing it in a cohesive manner or I think it’s really important. I’d say that the champions there has really been the ALS Association and the MDA with lots of patients in and their caregivers going together with a single voice of “this is what we need and that we’d like.” I think they’re still — we have to keep lobbying all the time but I think having a kind of clear message in that and a kind of a group approach would be great.

I would recommend people if they haven’t already that they reach out to their local ALS Association and MDA. They all have these advocacy teams and enough to join them so that we have more people behind it. If people do it all on their own, then there are different messages going through and it’s much less effective I think.

Caller: Thank you for doing the show today and taking the time. This is kind of groundbreaking and I’m excited to see this happen. Thank You.

Dr. Cudkowicz: You’re welcome. Thank you.

Seth: With that we will go to our next caller.

Caller: Yes. Hi, doctor. Thank you so much for taking the time to do this show today. You mentioned next generation sequencing. I have a question for ALS patients. I have several questions I guess. First, what is the cost to do that? Should patients request that diagnosis and then where is that available for ALS patients right now?

Dr. Cudkowicz: Those are great questions. I don’t think that today doing like a whole genome sequence is going to be that useful. Those costs have come down a lot depending on where one does it. They range from $2,000 to $5,000, but I think more important is to consider getting people’s DNA tests for the known genes that cause ALS. The reason I think that’s important now as opposed to maybe a couple of years ago is because there’s treatment being developed just for the genetic forms. It’s important I think for someone else, they carry any of the known genes because of these new therapies. I’ll be a little more specific.

One of the most common genetic causes of ALS is in the mutation with Chromosome 9. It’s called C9orf72. This causes 40% of ALS in the families but it also is found in between 5% and 10% of people without any family history. If you don’t have a family history and you don’t get tested, you have no idea if you’re carrying that particular genetic mutation. There are several companies working on ways to fix such genetic mutation. I think getting tested is more important.

Now, the challenge is that can be a very expensive test that ranges again from a couple of hundred dollars to a couple of thousand depending on where you live your insurance and which company is used. Hopefully, that cost will come down. As technology improves, the cost should come down.

Caller: Is this whole exome sequencing cheaper that whole genome sequencing?

Dr. Cudkowicz: I believe it is. I just don’t think at the moment like people would know what to do with the data. I think it’s useful on the research side for sure but clinically if — unless it’s one of the known genes, it would be hard to know what to do clinically with the whole exome or whole genome sequence results.

Caller: You said there were targets — people targeting that C9. Are there other neuron diseases like Parkinson’s that have that same genetic mutation?

Dr. Cudkowicz: Not Parkinson’s disease but the C9 mutation is also found in people with something they call Frontotemporal dementia as well as another illness called Spinocerebellar atrophy or ataxia. It does look like that one gene can cause different disorders, one of them being ALS. The gene was only discovered three years ago and now a lot of people working on it and very complex but I think the key is that we’re not that far from studies and people of a way to turn off a mutation. So I think it’s getting more important for people to know if they carry that gene or not.

Caller: Okay. Well, thank you so much for taking time to answer my question.

Dr. Cudkowicz: You’re welcome. Thank you.

Seth: All right. We will take another caller. Caller 3, please go ahead.

Caller: Hi. It seems to me that there are lots of studies and things going on– it seems like you have to be in the right location. Is there any way — it makes it harder for a person to be treated or to be studied if they can’t live, say, in Boston or in Massachusetts. What is the reason for this? Are there ways around it? Are there ways to make this one accessible?

Dr. Cudkowicz: One of the goals of our ALS Consortium, the NEALS Consortium is to have a center everywhere in the United States. We do have a hundred centers so there are many centers that are close to patients. But in some of the trials, they’re small trials so they can’t be at a hundred centers. I think the one you’re referring to is the Brainstorm study that’s just had three centers. It does make it — it makes it impossible for people who live afar from those areas to be part of that particular study. The hope is that with a hundred centers out there in the US who know how to do clinical trials, there should be able to be at least one if not more studies at each of these centers.

Caller: Okay. Thank you.

Seth: Thank you, Caller 3. We have time for one more question. We will go to Caller 4. It looks like we have lost them. Being a little cognizant to Dr. Cudkowicz’s time, we will wrap up here. I would like to ask Dr. Cudkowicz, is there anything else key that you think we have not covered here that our listeners should be aware of?

Dr. Cudkowicz: I want to make sure we kind of ended with what I think is the truth which is this is an incredible time of hope in ALS. There are thousands of people study now as opposed to a hundred or so a couple of years ago. It doesn’t go a week where there isn’t a meeting in ALS, it’s really a hot field and one where there’s a lot of hope. One of the challenges is keeping up with the information. I think your website and this type of groups are really critical for sharing that exciting science with patients and their families. So I’m very upbeat and hopeful that there are some big changes and big events are around the corner for people with ALS and their families.

Seth: Well, thank you very much for you time. We will have the transcript from this our inaugural show available one week from now. We will archive this show for those who were not able to listen today.

Please do follow us on alscrowd.org. We will announce our next speaker as soon as we have verified that. Again, sincere thanks to Dr. Merit Cudkowicz. Thank you for your time.

Dr. Cudkowicz: Thank you for having me. It’s great to talk to everybody.

About Author


ALS Crowd co-founder, friend and ALS patient supporter. Jenny launched the CrowdCare Foundation in 2012 to bring patient involvement into the acceleration of a cure for rare and orphan diseases.


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