Nancy Klimas, MD, a Clinical Immunologist and professor at Nova in the Karin Patel College of Osteopathic Medicine, Director of the Institute Neuro Immune Medicine, Assistant Dean for research at the Osteopathic Medical School and Director of the Gulf War Illness Program at the Minor VA Hospital talks about how veterans were affected by Gulf War Illness and the research that is being done to help them.
Interview conducted by Ivanhoe Broadcast News in May 2018.
What is Gulf War illness?
Dr. Klimas: Gulf War illness is very specific. In nineteen ninety and ninety one we sent eight hundred thousand US troops to the Middle East to fight in the first Gulf War. You might remember that Iraq invaded Kuwait and we came to the rescue with the rest of the world. And we had about a four to six-month prep time and then we had about a six-week war, and then we had a rather lengthy cleanup time afterwards. And in the window of that all those exposures, we sent these veterans to a very toxic environment. There was a lot of toxicity in that environment. They were wearing pesticide impregnated uniforms which turned out to be very toxic.
They were wearing what?
Dr. Klimas: Pesticides impregnated uniforms. And they were very toxic organophosphates. And whenever the SCUD missiles went over which was very frequently and the chemical alarms went off they had to jump into a plastic suit, a chemical protection suit which caused them to sauna in their organophosphate. They were using DEET, which is not very pleasant but they were using it at a hundred percent which you can’t buy even eight percent now, I think it’s the top strength. There were many, many other toxins they were exposed to depleted uranium through the armaments. There were exposed to a lot of vaccines and some of them had previously been untested. The anthrax vaccine, they were convinced that anthrax was going to be used. So they used a vaccine that hadn’t been through its safety trials. There was just a lot of different exposures. Anyway, the long and short of it is that out of eight hundred thousand troops some three hundred thousand veterans are now ill twenty seven years later so one in three came back ill and stayed that way.
What are the symptoms? What symptoms are they presenting with from these toxins?
Dr. Klimas: Actually that’s how I got into this was through that symptom complex because I take care of in research in another area called myalgic encephalomyelitis. It’s also known as chronic fatigue syndrome and the symptoms are very similar. They have profound fatigue, they have exercise intolerance and that’s an extremely unusual symptom in medicine. Usually exercise makes people better in most illnesses. But when the illness involves neural inflammation, often exercise makes them worse. Or if the mitochondria are screwed up, your energy pathway. So anyway they have profound fatigue, they have exercise intolerance, they have total body pain to the point where you can diagnose fibromyalgia in most of them. They have irritable bowel syndrome, their gut doesn’t work right. Rashes, chest conditions, just lots and lots of different symptoms all piled on the same person. And now twenty seven years later these things have escalated and they’re often in very poor condition because they can’t get up and move around and some times they’ve gained a lot of weight on account of that to boot, so it’s a miserable illness. And it definitely deserves some serious attention and research and hopefully effective treatment.
And out of the three hundred thousand, men and women are both afflicted with this?
Dr. Klimas: Oh, absolutely. It’s interesting because women were deployed to that war, about nine percent is the actual number, so roughly that percent we assume to be ill now. Part of our research here is to examine the gender differences, because women are often left in the dust of this kind of research. If ninety percent of people sick are men, the focus has been there. Certainly all the animal models are male animal models. So what we’ve learned about women we’ve learned from the actual veterans themselves, that’s actually pretty good science. And we have a very strong focus here in this research group to try to better understand and find effective treatment for women with Gulf War illness.
When they present with the symptoms was there any hard evidence and blood work that they were exposed to something?
Dr. Klimas: Well, we know what the impact was biologically. In terms of what is the biologic impact of this illness actually that comes to the story of why we have this consortia now. The last five years, there have been two funded Gulf War illness consortias. A contortion means you’ve got a group of scientists to work together instead of in competition with one another and hopefully that the parts add up to more than the sum of the individual. That’s the idea of a contortion. The CDMR, congressional directed medical research program at the DOD which is how Congress directly directs funds to a given illness. I think Congress has the NIH which they fund and a VA which has its own source of research funding and then this congressionally directed research medical program. Another way that Congress can be responsive to their community and direct something. So, the veterans went to Congress and said, we’re not getting anything from the NIH, we’re getting not enough from the VA, this was some years back, do something. Congress said, fine we’ll make a fund and they created this program and they pretty much kept It funded year-by-year but there’s been a couple lapsed years. But mostly every year they put money in this program. Five years ago their panel that decides the focus of where this investment should be, which is an extraordinary group of advocate scientists and policymakers that’s brilliantly conceived. And they really think about how can we get something back to the veterans as soon as possible. These people are sick now they want to find something for them not just studied what happened. That’s the idea. They funded these Gulf War illness consortia and we here at Nova got one of those consortia under the direction of Dr. Morse, Marianna Morris and a great team of scientists here. It’s actually what brought our group here. That was when we all left our universities and came to Nova to create this Institute, the institute for learning medicine was sort of born from this consortia award and we all came together. There was another consortia at Boston University that brings about twelve other groups of scientists together. We’re actually a part of that one too so we could communicate. Fast-forward four years, five years of research, it did exactly what was intended. Can we learn enough about the biology of these illnesses of this mixed up illness that we can direct treatment at what we understand of the biology instead of just continuously treating the symptoms of the illness.
In treating the symptoms, are pain pills a part of that?
Dr. Klimas: Yeah, symptomatic treatment is basically pain management, energy management, stress management it’s really not very effective. If someone gets reactive depression then you can treat that. Further if you think about what this illness actually is, it causes a lot of different integrated systems to find a new and sick balance. Our group is all about homeostasis. When you’re well your endocrine system, your immune system, your autonomic nervous system, all these systems are in this balance and they stay in this balance and for the most part in our lucky lives we stay in that balance. If we get a little sick with the flu, we get a little out of line but we always fall back into this balance. But it’s the right constellation of really rotten things happen to you, you climb up a mountain and you fall back into a new balance. And that’s what we’re perceiving happened in Gulf War Illness also, that’s why our focus is there. And for us to better understand how that balance worked we brought this huge group of people together, it’s just amazing. We have genomics with immunology, we have endocrinology, we have autonomics with animal modelers and the big, big score computational biology. Because then we can take all of this knowledge from each individual specialty and give it to these computational biologists who use what’s in like super computers to try to make sense of all the interactions and balance of the system. And then we took advantage of this key feature that they’re exercise intolerant and we put them on a bike and we measured before, during and after and measured the old cascade of events across all of these systems, all those genes. What gene gets turned on or off, whatever. Millions and millions of pieces of data per time point, eight time points in just four hours and one the next day. And from all that data the computational biologist not only are able to model the illness but the mediators of what causes it to persist or relax. Then, using super computers they could model intervention. So we’ve had this fantastic success of being able to take a really complicated illness, use the amazing new technology of these super computing systems and these genius computational biologists we work with and then create a model of these illnesses. Break them into their subgroups men and women. How do they break out biologically different. Within men comorbid PTSD or not. They break up biologically different. And then model an intervention for each subgroup. We did that and then we took it one step further in the mouse model for Gulf War Illness. We were able to take one of those subgroups and take the proposed treatment that the computers came up with and tested in this Gulf War Illness now aged out some years. So in a chronically ill animal, we were able to reboot all the homeostatic networks back to normal. So, we treated them with an intervention that was sort of an immune endocrine. And we got an immune endocrine autonomics everything back. It was very exciting.
How would this look in a clinical setting?
Dr. Klimas: We’re so close, it’s so exciting, I really find this to be one of the best examples of an amazing government investment, right. You’ve sent all these people off to war, they came back sick. In a very methodical way now the VA with a partner and I don’t want to leave the VA in the dust, cause they paid for a part of this. The VA and the CDRNP programs working together, came up with the funding mechanism and the insight to put out calls for applications that would draw teams like ours together. It was very clever, because they actually gave us a one year grant to write the grant. That was really neat. We actually got to meet with each other, we didn’t know each other, we just knew each other from our work. We met for long periods of time, hashed out our plans, got to know each other and become real collaborators and then write this amazing grant that was funded. And all of us relocated here and we pulled it off and then we cured a bunch of mice. Where we are now is exactly what they wanted in that period of time. They wanted us to go from ground to intervention space. And now we’re in the space where our first Phase I study is underway. It just got off the ground in the last couple of weeks. We had the first group of Gulf War Illness men where we’re treating in this way that the model in the mouse worked. And then we used the backload of all that science and the science from the Boston University group together, to write a clinical consortia grant to do a series of Phase1 and Phase 2 studies. To bring these mediator based interventions to treatment for these Gulf War veterans.
So you’re getting closer.
Dr. Klimas: Is it cool? I mean that’s only five years. That’s a lot of science in five years.
That’s a very fast. What do the treatments consist of?
Dr. Klimas: In this particular study we’re using a biologic intervention that is a monoclonal that blocks tumor necrosis factor, and I don’t want to use the name because it sounds like you’re advertising.
Give us another version.
Dr. Klimas: You don’t want people to go out and try to get this because it’s only Phase 1 and we haven’t got the safety done yet. But in the animal model we bring the inflammation in the brain down using a biologic that blocks information and if we bring it down by at least fifty percent, that’s what the model says, we should then make the endocrine environment in the brain healthier where it’s been very unhealthy. Then down at the level of the adrenal gland we block the receptors so that the signal from the brain can’t be heard, briefly. That causes the adrenal gland to send a feedback of saying louder more, more, more. But now for the first time, the brain can hear it because it’s not all noisy with inflammation. And now that whole endocrine loop in the brain, the hypothalamus pituitary loop, hears the signal and reboots at this better set point and then we release everything and it just goes. It’s pretty cool. So in the animal it was very quick. It was a short intervention, we gave them one dose of the biologic and we waited a week and gave them one dose of the blocking agent and it rebooted the system. So, pretty exciting.
Yeah. It’s rebooting the system.
Dr. Klimas: Yeah. It is rebooting, we’re rebooting. That’s exactly what we’re doing, trying to reboot homeostasis back to normal. And then hope it sticks. Now the human is probably way more complicated than the animal, you like mice to lead the way. But they have a history of not quite doing so. You’ve got to come in to the biology of it all. In our intervention in the first study we’re doing is a month of the thing that brings down brain inflammation and then a week of the thing that blocks the adrenal gland. That’s where we’re at.
A Phase 1?
Dr. Klimas: That’s our first Phase1 and that’s just one subgroup. In our consortia award this new one that’s going to allow us to roll out five more projects we’ll use that platform to roll out other subgroups and possibly other treatment strategies. And not just ours because like I say there’s another group in Boston that was also awarded this pre-clinical work. And they have a lot of ideas generating out of their group too. So we’ll use this consortia, it’s a five site consortia. We have Boston, the group in Boston and ourselves here at Nova. And we have the Bronx VA, Palo Alto and NSC. Anyway we have five sites it’s NSU, and the Boston University group, the Bronx VA, Palo Alto VA and New Jersey VA.
Is the idea that those who are suffering from Gulf War Illness can become part of these clinical trials, all over the country?
Dr. Klimas: Absolutely. We wrote this to be as inclusive as possible because there’s always some money limiting. But we wrote a budget that allowed people to fly in from out-of-state. We wrote a very healthy budget. So that veterans who aren’t in those catch areas can feel included in the opportunities that these studies would bring us. That’s not to say they aren’t already included. Our site already has a numbers study underway from this same work in an earlier stage. So that’s exciting, because right now we have a study that’s already Phase III, from work that was started from a group in San Diego, from Beatrice College Group using CoQ10 as an intervention to try to restore mitochondrial function. That’s a study underway, It’s at four sites. It’s available to veterans right now. We have a study that focuses on an intervention point that we discovered with all this biologic modeling work of ours. And then we used the safest thing we could find that touched it. We have a study looking at curcumin and glutahione in the Gulf War group. So that’s a study that’s underway and we’re recruiting right now at are site here. We have one of these reboot things already off the ground.
These common things and common talks.
Dr. Klimas: Well that is so cool because I love my competition because first, they give you the target. And remember, these are math guys, they’re physicists and engineers. They’re not biologists. But they can find the target. I love that they think in this open way and not be constrained by what I learned to be true. Because they’re actually testing this all mathematically. So in a very mathematical way they find the target and the three-dimensional structure of that target. Then they use confrontational biologists to see what sticks in the target. And they don’t give this a long list. And generally, there’s something really precise and incredibly toxic and expensive at the very top of that list. You know some biologic. And then somewhere around eight or nine or ten there’s some nutraceuticals on the list and I’m like okay I’m willing to use a repurposed drug because one of our goals is to get something to these guys right away. So if I use the drug that hasn’t been approved by the FDA yet it could be years. So instead we’re like stuck in that repurposed space so that we can just add a new label or find a new indication for a drug. And then if it’s a nutraceuticals and its effective we’ll jump on that because that’s one of the issues all these people have is access to knowledgeable healthcare. So if you find something that they can get themselves that would be lovely.
Do you see that biologic, the reboot, do you see that as a possible injection or a pill one day?
Dr. Klimas: Oh I think that the reboot thing works. And again it’s going to be subgroup by subgroup, it’s going to be short which is lovely. But it is going to be something probably an injection or something like that. For a brief not lifelong period and then a pill for a week or so and then hopefully maybe you’d have to retreat them again in a few years if it bounces back up again. But we’ll have a strategy to bring them back.
And how soon do you think these Gulf War veterans are going to get the help they need?
Dr. Klimas: That’s such a good question. Usually if you take something that we’ve invested a lot in like HIIV right, and found with a huge investment, we’re not talking small investment. We have known this was defined in nineteen eight four and had an effective therapy in nineteen ninety four, that was pretty fast; this is as fast as it’s ever done. Hepatitis it took thirty years, more thirty five from the time we knew what the target was to the time that we had an effective treatment. So generally speaking going from scratch, from Phase I to Phase III and available is a very long time. We have moved that time line up a lot. To say that we’re doing a Phase I and II trials aggressively now so that we can move to Phase III. And bless them both the VA and the CVRMP have provided Phase III strategies. So we don’t have to wait for pharmaceutical companies to want to join us, we can just get it done. And that is really the best gift that I can think of. So I can anticipate that if our phase, our first placebo control studies roll out okay, that we’ll be in the Phase III study within the next two years And then the Phase III generally only take about three years to go so about five years from now to be able to say that we’re at the point where we can say that this could become available as a treatment.
That’s really fast.
Dr. Klimas: Yeah, fast. It doesn’t feel fast to someone who has been sick for twenty seven years. And I’m so frustrated on their behalf because they have been sick for twenty seven years. But this is as fast as it could possibly be done. And I can at least give them that promise that no one has worked harder or faster to try to get them well than we and others in this field have tried to do.
(Discussion on animal testing and biologic testing) Is it possible to get that on tape and then I’ll research it and find out if it’s okay to use? Do you want her to say it differently?
Dr. Klimas: I’m trying to remember how I framed it before because I was basically saying we went from stem to stern so let me think about that. Okay, so basically what we’ve managed to accomplish in the four years of this consortia funding is going from a human model where we put people on a bike, drew blood, nine points in time over twenty four hours. Measured every gene that was turned on and off, all the regulation of those genes, all the side effects, all the hormones, all the cells and so on. Every system we could think of, endocrine, I mean on and on. And then mapped out using a computational platform, computational modeling, the whole dynamic of what happens first, second and third. Then the computational biologists were able to take that and model the illness in a way that they could actually do virtual clinical trials. That was very exciting. They came up with dozens of strategies. One of the things they learned is no one trick was ever going to work, we had to do two. Because you had to push one system like the immune and then another system like the endocrine in the right time course to make it all fall in to place. And then in essence we booted homeostasis back to normal. We tested it in a biologic system, it worked, we moved on to the human clinical trial which is under way right now. So on the strength of that and that was done in one of these subgroups we defined, we believe we can come up with an effective therapy for each of the subgroups that we defined. And that’s very exciting.
And the Gulf War illness and beyond because you have governments using chemical weapons.
Dr. Klimas: No better time than now.
Your research could end up saving people.
Dr. Klimas: I’m wishing you were in Syria right now because we know exactly what to do if this works to help those poor people that have been gassed in Syria. You watch those poor children with those neurotoxins used, the survivors have a bad future ahead of them.
This will show up later in other words and that could happen with these Gulf War veterans as well all these years later.
Dr. Klimas: Yes. It’s the organophosphate that they were exposed to in their uniforms is just one of their exposures, they were also exposed to Sarin. In the Gulf War we blew up Sarin depots that Iraq was holding, we literally bombed them to blow them up. And we aerosolized a cloud of Sarin. Dr. Morris that works with us was able to demonstrate that level of Sarin was enough to cause illness. That’s one of the reasons why she’s one of the top people in the Gulf War illness field.
How do you feel in this position and it’s your research?
Dr. Klimas: As a leader in environmental health. It actually changed the whole way we clinically approached things. It’s interesting watching the evolution of science driving the evolution of your healthcare. And our group here at NSU has a clinical program. And initially it was sort of an integrated group of inner-disciplinary people working together. But what’s happened over these last five years is we realized integrated means everything. We turned in to an integrative medicine program. And we have Dr. Erma Ray with us who’s now the president of The National Association for Environmental Medicine. That just shows what happens in just a few years that our focus has led us to discover how much human health whether or not you were in the Gulf War has been affected by the amount of toxicity exposure we have in our day to day life.
And that’s what drives you to do this?
Dr. Klimas: In part. Every time we are driven to do something initially it is because you’ve met an incredibly ill person and you thought you should be able to do something about this. And that’s what happened with NECFS for us as a group and for me as a person. But it’s definitely what happened with Gulf War Illness as well. We put these people in harm’s way and we have to do something; it’s not right. They went off, they volunteered, they did their duty and they came back and one in three are desperately ill. They’re really very sick and we need to take care of them.
Can Gulf War Illness be transmitted?
Dr. Klimas: It’s a really good question and it’s got to do with whether or not the DNA has changed that you transmit to the next generation. I actually had an agent orange person ask me if his DNA had changed and made his son at risk for Gulf War Illness. Because he had a very sick son and his was an agent orange veteran. And he came up in a public meeting and asked the question. I was just sitting there going, you know what we haven’t asked that question. That’s a question, that’s such a good question. Recently there was a study that was well publicized about the DNA change in those two twin astronauts right, that they might have been this headline right? It was like a ha-ha they’re not twins anymore. But it was a really big deal; this guy’s DNA had changed from ionizing radiation exposure in the atmosphere from the many months that he spent without the same level of protection that the atmosphere gives us. It was a very interesting question because his DNA has fundamentally changed right. The question is, and it’s an unanswered question, has the DNA in the in Gulf War Illness or agent orange or any of these toxic exposures that our veterans are dealing with actually put the next generation at risk. There’s certainly a group of veterans who believe that to be true. And there was an effort to do a multigenerational study some years back. But to do that kind of study you have to have literally thousands of people to be able to look at next generation affects. And I don’t think we ever reached the power we needed for the next study to be able to answer the question.
I didn’t hear much about Jimmy, can you speak to him?
Dr. Klimas: Jimmy gave me permission. And you’re going to be talking to Jimmy.
Yes, I think they’d like some background about how he was when he came to you.
Dr. Klimas: Right now I Direct the Gulf War Illness Clinic at the Miami VA. It’s a labor of love, I sort of created it without anyone asking me to, I think they found out later. Many of these people were coming in sick and I was the obvious person because I was taking care of the chronic syndrome patients and so I just started getting the referrals. And eventually I just created this clinic. And there’s hundreds of people in this clinic. That’s where I first met Jimmy. Jimmy found me, he didn’t come in by accident he’s actually from Orlando so he had to go to some effort to get the referral. And he was typical. He was a Gulf War vet that had lots of exposures. He’s extremely knowledgeable about the illness, and he was frustrated that he hadn’t found anyone who knew much about the illness. And that’s pretty typical, we wish they did have more knowledgeable people. But the truth is until you have evidence-based guidelines to treat an illness that’s based on science it’s awful hard to have a program that every veteran can find. So instead they seek out investigators like me that are maybe a little ahead of the curve because I dream this at night. And that makes a difference. Anyway, Jimmy sought me out and I think we did help. And the one thing that I can say about Jimmy is I call him a super user he volunteers for every study which is lovely which means I know a lot about him. Because he got on the bike and I can look at his gene profiles and I can look at all that immunology and endocrinology.
And he can talk about what he’s doing?
Dr. Klimas: Yes.
And these are double blind studies?
Dr. Klimas: Mostly, the way studies usually work is in the first Phase its open label. Just because we’re just trying to see if there’s any affect at all. And then if you have that little hint that you should go on then you design the more powerful study that’s placebo double control.
If someone out there sees this report and want to learn more or they know someone or they want to join a trial is there a website that we should point them to?
Dr. Klimas: Yes. Its http://www.nova.edu/nim/index.html and there you will find every kind of scientific endeavor we’re attempting.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Precious Leaks-Guiterrez, Community Outreach Coordinator
305-575-7648
Marla Oxenhandler, Media Relations NSU
954-770-9204
Sign up for a free weekly e-mail on Medical Breakthroughs called
First to Know by clicking here.
