• ALS Crowd Radio Episodes
    • Aug 26, 2014

    ALS Crowd Episode 5: Dr. Nazem Atassi on Advanced Imaging for ALS Therapy Development

Nazem Atassi, MD
Associate Director NCRI at Massachusetts General Hospital
Assistant Professor of Neurology at Harvard Medical School

Interview date: Wednesday, August 27, 2014

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We talk with Dr Nazem Atassi, MD, of Massachusetts General Hospital about Advanced Imaging for ALS Therapy Development

Full Transcript:

Seth:Hello and welcome to Episode 5 of ALS Crowd Radio. I’m your host, Seth Christensen, here as always with my co-host, Amy. We are really excited about today’s show. We have Dr. Nazem Atassi from Massachusetts General Hospital with us to talk about advanced imaging as a means of ALS therapy development. Amy?

Amy: Dr. Nazem Atassi, Associate Director at Neurological Clinical Research Institute at Massachusetts General Hospital Assistant in Boston, Massachusetts, Assistant Professor of Neurology at Harvard Medical School, completed Neurology training at Boston University Medical Center and Fellowship in Neuromuscular Disorders and Clinical Trials at MGH. He received his Masters of Medical Science in 2010 from Harvard Medical School. Dr. Atassi is the Co-Chair of the Upper Motor Neuron Task Force at the Northeast ALS Consortium and he serves on the Advocacy subcommittee of the ALS Research Group. Dr. Atassi received several awards including the MIT 100K Life Science Award from Massachusetts Institute of Technology, the Anne B. Young Translational Neuroscience Fellowship, and NIH K23 Career Development Award. He is the Primary Investigator for several research projects focusing on ALS and PLS clinical trials and neuroimaging. Dr. Atassi attends two clinics at MGH — ALS Multidisciplinary Clinic and Neuromuscular Clinic.

Seth: Dr. Atassi, welcome to ALS Crowd Radio.

Dr. Atassi: Thank you. It’s a great pleasure to be on your show.

Seth: Well, we are really excited about today’s topic. I think imaging is a little understood area in the ALS community. Before we get into that specific topic, we always like to open our show with the question, what do you think the cause of ALS is?

Dr. Atassi: That’s a very good and a very complex question. I think we could say that ALS is inherited or runs in families in about 10% of the cases. In the minority of the cases, there looks like a genetic component or a strong genetic component. In these cases, in the 10% cases, we know the causative gene in more than half of those cases. So we can say that for the ones that we know the gene that actually we know the cause of the disease, that the cause of the disease is that gene and whatever the protein that that gene makes or doesn’t make, fails to make, is the cause of the disease.

On that aspect, there is a great, new development, new research, things that we learned from the new gene that were discovered in the past few weeks — sorry, from the past few years in ALS, specifically the C9ORF72 gene that was discovered in 2011. So we could comfortably say that we know the cause of the disease in these specific cases.

Now, for the majority of patients with ALS, it doesn’t run in the family, so 90% of the time, it doesn’t run in families. In these situations, we call it sporadic ALS. For sporadic ALS, we don’t know the kind of root cause of the disease, but we believe it’s a combination of maybe some genetic predisposition in addition to some environmental factors. What we know from pathological studies on people who passed away from the disease and also on animal models of the disease that there are certain themes that we see in terms of disease mechanisms. I’m just going to mention a couple of these themes and maybe we can talk in detail on some of them as well.

Seth: Great!

Dr. Atassi: One of these themes is called excitotoxicity. That means the hyperexcitation of nerves. This involves a chemical on the brain called glutamate. Glutamate is a chemical in everybody’s brain and its job is to stimulate nerves. When there are large amounts of glutamate, more than needed, then the nerves are overexcited. And when they’re overexcited, they can’t keep up and they start dying, so that’s one of the proposed mechanisms that contribute to the disease.

The other proposed mechanism is energy metabolism, so this functions in the energy balance in the cell. This goes to small organisms inside the cells called mitochondria. These are the cell energy factories that make energy basically inside the cell. We know for sure that these are clearly effective very early on in the disease. In addition, if you want to relate to the metabolism issue — we know that for example, if you give the animal model of disease, if you give them a high fat diet, a diet that is high in the content of fat, they will live longer compared to animals that were given regular diet, so something has to do with energy. Something has to do with diet, with fat that also related to the disease.

There are also other factors that contribute to the disease. We know that there are some accumulations of certain proteins that we see in the brain and these are toxic to the brain, in addition to neuroinflammation, which is also a main component that we see across the board in people and in the animal model of the disease.

Seth: Now, on the topic of inflammation, do we know if inflammation actually is the causative factor in degeneration or is it a harmless byproduct?

Dr. Atassi: We don’t know for sure if it’s causative or not. There are some genetic discoveries that hint to the fact that inflammation could be causative or actually an important contributor to the disease. At the same time, it’s definitely not like a stander-by that it’s doing nothing and I can tell you why. If you look at human pathology, if you look at basically studying the brains of people that passed away from the disease, you would see a few things. You would see that there are definitely increased inflammatory cells that are called microglia in the brain. When you see this increase in the inflammatory cells, you see them around in the diseased nerves. These are the nerves that are dying basically in the disease. They are degenerating nerves, so that’s one piece of information.

The other piece of information, if you look at the number of B-cells and you look at how fast the disease progressed in these people, what you would see is that the higher number of these inflammatory cells, the faster the disease was progressing in these people. So not only that we’re seeing increased inflammatory cells in people with ALS, not only are we seeing the increased inflammatory cells around the relevant degenerating nerves, the nerves that are dying because of the disease, the motor nerves that control the movement, but also the number of cells has to do with how fast the disease was progressing. It’s a very strong link between the inflammatory cell and the disease, and this is from human pathology, from basically data that comes from people.

Now, if you look at animal data, the advantage of animal data is that you could basically sacrifice the animals very early on in life. What you could see is that inflammation or these inflammatory cells is probably actually one of the earliest changes that you see in these animals and in the brains of these animals. So even long before these animals develop any muscle weakness or any symptoms at all, maybe just like a few weeks after birth, you would start seeing these inflammatory cells going around motor neurons. That’s telling you that basically, inflammatory cells have to do with the initiation of the process. It doesn’t tell you the main cause, but it’s like a very early contributor.

The other thing is that once the animals develop weakness, you see an increase in these inflammatory cells around the same nerves, the motor nerves. As the weakness progresses, the number of inflammatory cells increases. The bottom line, if you look at both data from people, humans, and data from animals, you would see that actually inflammation occurs very early in the disease and probably long before symptoms develop. Once the symptoms develop, then inflammation actually increases as the disease progresses and inflammation corresponds with the severity of the disease and the rate of progression. All of these are basically telling us that inflammation is not just a passive stander-by. It has to do with the disease initiation, disease progression process.

Seth: Do we know whether these inflammatory cells are uniformly located in the brain and the spine of ALS patients?

Dr. Atassi: What we know — actually, there was a very well-done study, I want to say, a recent one that looks actually at 60 different autopsied brains from people who passed away from ALS and they looked systemically at the motor cortex. This is the area that controls movement, and then the nerves that comes out of it, so they looked at the subcortical areas. They looked in the medulla, which is the area that controls the movement of the mouth and tongue, so this is the bulbar aspect of the disease. They also looked in the cervical spine. That’s the part of the spinal cord in the neck, and they looked at the lumbar spine, the part of the spine that is in the lower back that controls the legs.

What they saw is there’s actually increased inflammation across the board in these patients in all of these areas that I just mentioned, in the motor cortex, at the top of the brain, in the medulla that controls the mouth and tongue and swallowing, the area in the spinal cord that controls the arms, and the area in the spinal cord that controls the legs.

They also found that these inflammatory cells are actually both in the grey and white matter, so the inflammation is actually relatively widespread in the brain and the spinal cord and involves both the grey and white matter. It’s specific to the areas that control the movements, but it’s not localized in a very small area. It’s really widespread.

Seth: Do we know whether we can affect the inflammation in any way through behavior or medication or sleep?

Dr. Atassi: That’s a very good question. I think that we should be able to affect inflammation. Why am I saying that? There are large numbers of drugs that target inflammation both on the market and also in discovery, in drug discovery. We just need to figure out which one of these is basically effective in the brain that reach the brain and are effective specifically for people with ALS. The bottom line is that we have a large number of candidates that what we need is an efficient way to screen these candidates. Now, how do we screen candidates? We know that inflammation is important. We have a list of anti-inflammatory medications, so medications that change immunity or inflammation, so how do you screen these medications? How do you know which one works and which one doesn’t work? Well, you have a few ways to do it. One is to use a disease model. The other way is like an animal model or like a cell culture model. The other way is to try to screen these treatments in people and people who have the disease, so doing clinical studies in people who have the ALS by trying these medications. If you use the disease model like an animal model, usually a mouse model of ALS, it is efficient because these mice are not very expensive and you can buy a lot of them. You can test a lot of them. I can test different medications on a lot of them. However, we have to remember that these mice are all based on a gene called SOD1 gene that only represents 2% of ALS population. That’s one issue, is you’re trying to test something on 2% and then take it from there and try to generalize it to the 98% or 100%, so that’s a big issue. The other issue is that mice are actually very different than people. You test something on the mouse. Even if it works on the mouse, that doesn’t mean that it’s going to work for sure on people. There are a lot of differences in biology. There are a lot of differences in dosages and kinetics of drugs between people and mice. So you can see the limitations and challenges of using these models for drug screening.

Now, these models are important. We learn a lot about the disease from these models. These models are probably important to test the mechanism of action, but in terms of predicting response in people, probably these models are not as good. Now, the alternative is to screen these drugs in people and people with the disease. The problem is that this is very expensive and very time-consuming, so clinical trials are very, very, very expensive. Now, is there a way to make this process more efficient? Yes, and this really is my focus of research. This is my research focus, is trying to find ways to screen medications quickly and efficiently in people with ALS.

Seth: That is an amazing segue to your own research. We will really quickly give Amy a moment to invite callers.

Amy: For those of you listening in today who have a question for Dr. Atassi, please dial 516-590-0362 and press 1 to indicate that you have a question for us at the end of this show.

Seth: Thank you, Amy. Now, Dr. Atassi, could you tell us what the focus of your research is today?

Dr. Atassi: The focus of my research really is to use advanced imaging technology to accelerate the process of ALS drug development. So my ultimate goal is to give treatments to people as quickly as possible. I can give you a few examples.

For example, now — and you’re probably very familiar with this technology — now, we have an advanced imaging technology using PET scans, so Positron Emission Tomography technology. What we could do is basically inject a radiotracer that goes to the brain and would only light up if there’s inflammation in the brain. Actually, it can detect these inflammatory cells and light up and show us that basically there are inflammatory cells in the brain. It tells us how much and where in the brain we see these inflammatory cells. This will allow us to measure inflammation in the brain in people living with ALS. It might sound simple, but this is a huge advancement in our knowledge. The fact that we could measure and localize accuracy inflammation in the brain in people living with the disease is not something that we could have done sometime ago. It’s really very exciting being able to do that.

Potentially, what we could do is we could take a picture of the brain, measure inflammation before somebody takes an experimental medication, an anti-inflammatory medication. And then that person could be on a course of a treatment, anti-inflammatory treatment for a few weeks or a couple of months. After that, we can take another picture of the brain and see if that inflammation goes away, decreases, or unchanged.

If the inflammation goes away or decreases, that means a few things. That means that our anti-inflammatory drugs, that candidate got to the brain, got to where it’s supposed to go in the brain to the target, and modulated that target, reduced the inflammation, did the job that it’s supposed to do. This medication’s job is to reduce inflammation. We can tell that this medication actually did reduce the inflammation, so that’s a good drug to take to the next phase, which is basically testing this drug in a very large number of patients and actually over a very long period of time.

At that time, what we want to look at is clinical benefit. We want to be sure — of course, it’s great to reduce the inflammation on the picture, but what we really want is slowing down the disease, stopping the disease, reversing the disease, so we need clinical measures, not imaging measures.

What the imaging measures help us with is the stat screening process, so if you have a large number of candidates, you can screen them one by one quickly and efficiently and accurately using these imaging technologies. Again, inflammation is one of them, but we have imaging technologies to look at the excitotoxicity that we talked about. We have other ones that can look at energy, so all of the mechanisms that we talked about. Actually, we have some kind of an imaging technology that can tackle that mechanism of action, so all of this is basically mechanism-based imaging for people with ALS.

Seth: Amazing! So this is the focus of your research today. What stage of study are you in? Are you actually imaging patients today?

Dr. Atassi: Yes. Actually, we received an NIH grant recently to image a number of people with ALS using this radiotracer to look for inflammation in the brain. The first step is to see basically the difference between people who have ALS and people who don’t have ALS, healthy volunteers, to see basically the difference in the amount of inflammation.

We clearly see increased inflammation in the brain, in the area that controls the movement in the brain, the area that we’ve known from pathology that has a lot of inflammatory cells. What we’re seeing so far actually matches exactly what we’re seeing in the animal model, what we saw in the animal model and in human pathology, so this is very, very encouraging.

The next step is we want to know if this signal changes over time as the disease progresses or not. So in order for us to asses if a drug is working or not in imaging before and after, we need to know if we don’t have any intervention, how the signal changes over time. This is where we are in research right now. We’re trying to image people at different time points over time to see how this signal changes over time.

Once we figure this out and we see that this is a reliable signal that we could use for testing the efficacy of drugs, the next step would be to start screening medications and see which one of these medications reduces that signal. We’re definitely in the middle of all of this. Again, we scan a large number of people. We’re now in the process of scanning some of them longitudinally, so over time.

Seth: For those of our listeners who are on the edge of their chairs right now, is there an opportunity for these listeners to be involved in your project?

Dr. Atassi: Of course. Our project is open. Obviously, there is an inclusion criteria and exclusion criteria and this is mainly for safety, for people’s safety. For example, if somebody has any contraindication for an MRI, again, this is a PET-MRI study. We do actually the imaging acquisition for both the PET component that shows the inflammation and the MRI component that gives us the kind of very high resolution anatomy. Any contraindication for an MRI, anything that’s telling us that the person is not safe to be in an MRI machine basically would be a contraindication, but the research is open.

It’s only available actually for this specific study in Boston at Mass. General Hospital, but I want to say that there’s a lot of research going on all across the US and Europe and other places in the world. Listeners can be actually involved in research in many different ways. One way to be involved in research is advocacy, advocating for the disease, educating people about the disease. We have the ALS Advocacy Day in DC that happens usually once a year where people go and talk to the senators to raise awareness and funding for ALS research.

There is the work that you’re doing with increasing awareness. We have our Northeast ALS Consortium. We have a Clinical Research Learning Institute where people come in and it’s a course. It’s an institute. They spend two days with us. People with ALS, they come with their family members and they learn all about research, all about advocacy, and then they become ambassadors for ALS research advocacy, so advocacy is definitely one way. Listeners or people can participate in the Ice Bucket Challenge. It’s a great example as well, so this is definitely one way to be involved in research.

The other way is to participate in research studies, to be basically a subject. We call them a subject basically in the study, so this could be an experimental drug trial. It could be a biomarker study where we collect blood or spinal fluid samples. It could be an imaging study similar to what we talked about. We learn a lot. We learn a ton actually from all of the studies whether we’ve given medication or not. This is something that definitely we cannot do without patient participation.

You can get very smart people in one room. They can sit and think and talk about so many things. They come up with all great ideas, but if you don’t have patients participating in research, we’re not going to get anywhere. This is definitely a journey that we have to take together. Participating in research is definitely needed and that’s another way to be involved in research.

Another way, actually the third way is to fund the study or the research program. This could be a small amount of funding or it could be a large amount of funding depending on the capacity of the person. In addition to NIH, National Institute of Health, and the foundations that fund some ALS research, we actually heavily depend on philanthropy and private donations to do our research. This type of funding actually is very important. It bridges a knowledge gap and it does actually the ALS drug development. What it does is it serves de-risking drug development for ALS.

Actually, it becomes attractive for the industry. Then pharmaceutical companies and biotech companies can take it forward. Again, funding and philanthropy is another great way to be involved in research. I want to say that each one of us can find a way to contribute to research either by advocating for research, participating in research, or funding a research study.

Seth: Dr. Atassi, you are the associate director of Mass. General’s NCRI. Could you tell us a little about the mission of the NCRI?

Dr. Atassi: Yes. The mission of NCRI is to develop treatments as quickly as possible to people with ALS and other serious neurodegenerative disorders. How do we do that? We do that through conducting efficient clinical trials. The NCRI has different functions. One of them is we have data management, project management, and electronic data capture system group. These groups, actually what they do, they run multicenter clinical trials for ALS and other neurodegenerative diseases.

Also, we have a site, a wing, or arm to this NCRI where actually we see patients. We do all these clinical trials. We do imaging studies. We do biomarker studies. For example, we have a very active clinical research program at MGH and some examples are from ALS basically, the trials. We have ongoing trials for a drug called mexiletine. We have the BrainStorm or NurOwn Clinical Trails. We have a GSK Clinical Trial going on. We have a trial for a drug called arimoclomol. We have the Neural Stem Clinical Trial. We have an exercise study.

All of these are ongoing and all of these are very active clinical trials for people with ALS, and we have a lot of other basic new trials in the pipeline. We have Actemra, retigabine, inosine, and others. All of these are in the pipeline for clinical trials in ALS. So the NCRI is really a very busy group laser focused on drug development for ALS and other neurodegenerative diseases both in terms of doing research in patients and in terms of running multicenter clinical trials.

Seth: For those of our listeners who are unfamiliar with the NCRI, this is MGH’s Neurological Clinical Research Institute. We will pause for a moment for Amy to invite listeners.

Amy: Hi, listeners! The number to call in is 516-590-0362 and if you have a question, press 1 so we know and we can answer your call.

Seth: Great! Thank you, Amy. Dr. Atassi, for our listeners all over the United States, do these studies you just mentioned only recruit in Boston?

Dr. Atassi: No. Actually, most of these studies are multicenter clinical trials, so these studies usually are run in different centers and usually distributed across different clinics in the United States. I would say there are a lot of different resources where you can find out about these studies. I’m just going to mention a couple of them.

One of them is clinicaltrials.gov and this is the FDA website. You could actually search by disease by which trial is active, which trial is non-active, which one is recruiting, which one has finished recruitment, so that’s one way to find out if there’s a clinical trial for ALS that is close to you.

The other great resource is the Northeast ALS Consortium website. I believe it’s alsconsortium.org. In this website, actually you could just enter your zip code on the website and you could say that “I’m looking for a clinical trial for ALS and I’m willing to travel.” They’ll give you options, 5 miles, 10 miles, 50 miles, 100 miles to go to a trial center and it will basically give you a map, a Google map where the trials that are recruiting that are next to you within the distance limit that you set, so it’s a nice, user-friendly tool to find out about research, what’s going on in the ALS research, and also what sites are enrolling for which trials, and if any of them are close to you.

Seth: Thank you. Very specifically, if our listeners wish to be involved in your imaging study, how do they apply?

Dr. Atassi: The best way to apply is to send an email. I’m not sure if my email is on your website or not.

Seth: We will make sure it is available.

Dr. Atassi: My email is natassi@partners.org, so you can send me an email if you’re interested. Alternatively, you could send an email to the study research coordinator. Her name is Julia Yasek and her email is jyasek@partners.org as well, so you could either reach me or her and we’ll be happy to facilitate scheduling to visit.

Seth: Now, is that for both ALS diagnoses and otherwise healthy patients?

Dr. Atassi: Yes. Actually, for this specific imaging study, we are open to — we’re accepting people who have the disease and also we’re looking for healthy volunteers to enroll in the study as well, so yeah, for both.

Seth: Wonderful! Thank you. We will now go to our phone lines and receive some questions from listeners. Listener one, you are on the air with Dr. Nazem Atassi.

Caller: Hi, Dr. Atassi!

Dr. Atassi: Hi!

Caller: My question is kind of multifolding. I am wondering with all this great research going on, how often do researchers across the country actually share their research or things that could help one another and build off of that, or is that more of, “We’re going to focus on this stuff and we’re going to see how that goes,” even though it might be helpful for someone somewhere else in the country, a researcher, I don’t know. So how much is information shared?

Dr. Atassi: That’s a great question. It’s something that we always think about and we always try to address, and I’m going to give you a few examples of how we share information. One way to share information is to publish the results of studies, so we do submit to peer review journals and we submit articles and papers. This is one way to share our research with the community in general, with the research community in general.

The other way to share research is we go to meetings and we also submit abstracts. We present posters and we give presentations in these meetings and we talk about our research. We share it with the other members of the scientific community and we get their feedback and we get their thoughts on our research.

We also share our research with the patients through talk shows like this, through all kinds of media. We share information, for example, to Northeast ALS Consortium. It has a hotline that you could call and you could talk to somebody about research. We also give a lot of presentations, usually sponsored by certain foundations and sometimes family to just talk about these most recent advances in research. These are all types of oral and written communications about research that we do.

There is another way that actually we collaborate and share information, which is basically we share data. That’s another level of sharing information, is sharing the actual data, not the result of the data, but the actual data, an actual sample.

I can give you two examples of this. In terms of data, we work with a nonprofit foundation called Prize4Life, and we came up with — we pulled together the largest database for clinical trials for people with ALS, which is called the PRO-ACT Clinical Trial Database. It has over 8000 patients that were called over time with a lot of information, including clinical information, labs, medical histories, medications, you name it, so it’s a very rich, very important data set that is actually publicly accessible, publicly available for researchers.

The Northeast ALS Consortium also has a huge biobank, a huge bank of samples from people with ALS, spinal fluid samples, blood samples, serum, urine, you name it. All of these samples are also available and all of these samples are shared and being shared and will be shared. They are there to be shared, so we definitely share data and we share samples as well.

Caller: That’s great. I’m wondering. In your opinion, what is the biggest hindrance to finding a cure for ALS?

Dr. Atassi: That’s a great question. There are actually multiple challenges that we need to overcome. Some of them have to do with how rare the disease is and that’s a challenge that is actually a little bit difficult to tackle. When you recruit for an ALS study, it’s usually not easy because the disease is rare. If you’re recruiting for a diabetes study, you can find a lot of people with diabetes. Believe it or not, it’s not easy to find people with ALS. I think advocacy, encouraging people to participate in research is one way to overcome this challenge.

The other big challenge is translating discoveries in the lab to treatments to people quickly. This is a multifold challenge. One has to do with the pharmaceutical company’s interest in the disease. It’s a challenging disease. It’s an orphan disease, so it’s not very attractive from a financial perspective for companies to invest a lot of money in this disease, although there are some companies that are investing money in this disease. When I say invest money, that means doing research, invest a lot of money to do research in a disease.

Again, this is where I mentioned a little bit earlier how philanthropy money and foundation money and NIH money can help basically bridge that gap and de-risk the drug development for the drug company, so then it becomes more attractive for them to actually consider ALS as a disease that they want to find treatments for. There are multiple challenges. It can be overcome by, as I said, advocacy and more sources of funding.

Caller: All right. Thank you.

Seth: Thank you, Caller 1 and thank you, Dr. Atassi. We will now go to our next caller, the number ending in 4475. You are on the air.

Caller: I’m on the air, yes, thank you. Dr. Atassi, I have a question about the SOD1 mouse model that’s been typically used. As you said, the familial ALS only affects a small percentage of the population, so do you feel that using this kind of a mouse model might mask the results on sporadic ALS situation? And then as a second question, is there any effort currently going on to develop a non-SOD1 mouse model?

Dr. Atassi: Yes. You made actually an excellent point with the first question. The point is if we’re going to use this mouse model, the SOD1 mouse model that represents only 2% of ALS, if we’re going to use that model to screen therapies, you are worried, you are concerned about missing a treatment that actually is effective in people, but not effective in mice. So having a negative study in mice would trigger basically not testing that medication in people, though it might be effective in people, and that’s an excellent point. That has to do with, as I said, the limitations of this mouse model.

Now, just to expand on this mouse model, this is a great mouse model to really help us understand the disease. A lot of the things that I mentioned about inflammation, we relearn these things from the mouse model. We’ve seen the inflammation early on in the disease. We’ve seen how inflammation increases as the disease progresses. We’ve seen all of it, so we learned a lot about not only inflammation, but other mechanisms from this mouse model, so it’s a great learning tool.

Now, is this the perfect model that will translate efficacy in this model to efficacy in humans? The answer is “no”. There are a lot of medications that worked in this mouse model, but when we took them to people, it didn’t work. That means if you see something that works in the mouse — when I say “works”, I mean prolonging survival in the mouse or slowing down the disease progression or the weakness progression. If we something like this in the mouse, that doesn’t necessarily mean that it’s going to do the same in people. In that respect, the mouse model is not the perfect model to screen drugs because when it’s worked in mice, it didn’t work in people.

Now, going back to your second question, are there any mouse models that are being developed for ALS? The answer is yes, there are mouse models that — attempts basically for mouse models that are being developed for ALS that are different than the SOD1 mouse model. The issue is that these mice, first, they’re still under development, so they’re not very well standardized, qualified, tested, so they’re still in the development stage. It’s not easy to make a mouse model.

The other issue is that it probably will suffer from similar issues as the SOD1 mouse model because they’re all based on genetic mutations. Now, if you have a mouse model that is based on the C9ORF72, this is the most common mutation that we know that causes ALS. It’s responsible for about 30% of people who have familial ALS and about maybe 5% of people who actually have sporadic ALS, so this is the kind of — if you’re going to build a mouse model based on a gene, that’s the gene to build it on because it’s the most common, the familial, and actually you can see it sometimes in people who have apparently sporadic disease.

That mouse model might be a little bit more helpful if it succeeds than the SOD1 mouse model. Again, we’re talking about their effect in predicting response in humans. This is the issue, but these mouse models are very important for us to understand the disease and the mechanism of the disease.

Caller: Thank you.

Dr. Atassi: You’re welcome.

Seth: Thank you, caller. We have time for one more brief question. Caller ending in 6431, you are on the air.

Caller: Yes, Dr. Atassi, thank you so much for what you’re doing is so exciting. My question was as you pre-screen or you did the baseline for inflammation and then there’s a treatment ongoing and then a measurement, do you have to judiciously make sure a certain time lapses? Are there any negative side effects to the imaging?

Dr. Atassi: Excellent question. I hear two different set of questions, one is basically what happens and how long we should wait between the two imaging, between the two pictures that we’re taking, and then the other question, are there any side effects of imaging, so let me answer the first question.

I just want to be clear that currently, we’re not testing treatments and looking at the effects of these treatments on imaging. This is the next step. Now, we’re in the process of characterizing the measurements itself, the imaging measurements itself and people with the disease. The goal is to test treatments quickly in people using these imaging technologies, so this is not ongoing. The testing of medications using imaging, it’s not happening as we speak today, but it’s going to happen very soon.

The question about time lapse, yes of course, you need some time lapse to be sure that the medication reaches a steady state, that the medication reaches the brain, reaches the area in the brain, and start to have an effect, so it’s not going to be take a pill — you’ll get an image one day and then you take a pill, and you take the image the second day and you’re going to see a change. Probably it’s going to be a period of treatment of two months probably or three months or something like that. It would just give the medication time to work and to reduce the signal.

Now, your second question about any side effects of MRIs or PET scans, again, we’re doing this study with a combination of scanner. It’s a scanner that has actually both the MRI and the PET imaging coming together. MRIs are actually relatively safe. MRIs are used on a routine basis in many different places and actually there are no known risks of being in a magnetic field. MRIs are not x-rays, so there’s no radiation in MRI, just a magnetic field. There are no known risks for the MRI except for people who have claustrophobia or have difficulties getting to the MRI.

The PET component, the Positron Emission Tomography component, that involves some kind of radiation because the tracer that we inject, it’s radioactive. Now, the good news is that it’s very fast decaying. That means the radioactivity goes away very quickly. It has a half life of 20 minutes, so within a few hours, the whole tracer is actually gone from your system completely.

The amount of radiation that a patient gets from doing a PET study, these types of PET studies, is the same amount of radiation that a person would get from walking around a city like Boston for a year from the sky. We all get radiation from the sky all the time. It’s really a minimal amount of radiation and risk of radiation that we get basically during the scanning time, which is about two hours.

Caller: That is so helpful. Thank you so much. Again, we just are grateful for your involvement, just for what you’re doing for ALS families. Thank you.

Dr. Atassi: Thank you. Thanks for calling.

Seth: Now, we know that Dr. Atassi has a number of people waiting to douse him in ice water, so we will let him go, but Dr. Atassi, any final thoughts before we wrap up?

Dr. Atassi: No. I just want to thank you so much for inviting me to your radio show. It’s really very exciting. I always love to connect with people, with patients, and I always love to share my research and everyone’s research with the patient. Again, I think the message or the important thing is that we’re in this together basically for ALS research.

ALS patients and their families, they can’t do anything on their own, and researchers and scientists, they can’t do anything on their own. The only way to make this work, the only way to find a cure for this disease is to work together, so I really value what you’re doing. It’s basically bringing researchers and scientists to connect and talk to patients, so I think that’s amazing, so thank you.

Seth: Thank you for our listeners. A full transcript of this interview will be available in a week. Thank you to Dr. Nazem Atassi of MGH. Have a great Ice Bucket experience.

Dr. Atassi: Thank you.

About Author

Seth Christensen

Seth is an ALS patient and founder of ALS Crowd, a division of the CrowdCare Foundation. As host of the ALS Crowd Radio show, he interviews top ALS researchers and focuses his efforts on the aggregation of big data to help researchers and patients find clues that will drive to a cure.


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