ALS Crowd Radio S2:E3 Dr. Paul Cox, PhD, Institute for Ethnomedicine: Environmental Causes of ALS

Dr. Paul Cox, PhD
Brain Chemistry Labs – The Institute for Ethnomedicine
ethnomedicine.org
Interview Date: April 28, 2016

S2:E3 Dr. Paul Alan Cox, Ph.D. speaks about his research approach in studying people to find and fight the environmental causes of ALS.  His research has proven the strong correlation between exposure to an environmental toxin called BMAA and ALS related symptoms.   Large doses of the dietary amino acid called L-serine may reduce the risk of BMAA exposure and delay the onset of symptoms.  Dr. Cox explains the phase 1 trials that have already taken place for L-serine and the urgency to move to phase 2 trials in 65 patients.  For more information, see ethnomedicine.org. 

ALS Crowd Radio Episode with Dr. Cox:

Full transcript:

Seth: Hello and welcome to ALS Crowd Radio Season 2 Episode 3. I am your host, Seth Christensen, here with my co-host, Lori Wangsgard.  

Lori: Welcome to this show. Throughout our discussion with Dr. Cox if you have a question please dial in at 516-590-0362 and then press 1 to indicate that you have a question and we will get to you. Now, I would like to give a proper introduction to our guest.

Dr. Paul Alan Cox is a Harvard Ph.D., Paul Alan Cox has spent his career searching for new medicines by studying patterns of wellness and disease among indigenous peoples. For these efforts, TIME magazine named Cox one of 11 “Heroes of Medicine.” His work with indigenous peoples in preserving their island rain forests won him the Goldman Environmental Prize. Cox has published over 200 scientific papers and four books.

He has held academic appointments at the University of California, Berkeley, Brigham Young University, the University of Melbourne, Uppsala University, the Swedish Agricultural University, and the University of Illinois, Chicago, and served as Director of the Congressionally-chartered National Tropical Botanical Gardens in Hawaii and Florida.

Cox founded Seacology, the world’s premier environmental non-profit organization for island conservation, headquartered in Berkeley, California. Through partnerships with indigenous people, Seacology has now saved over 1.3 million acres of island rainforests and coral reefs in 56 nations. Throughout Polynesia, he is known by the chiefly title Nafanua.

Cox currently serves as the Executive Director of the Institute for Ethnomedicine in Jackson Hole, Wyoming. His research there is focused on finding and fighting the causes of neurodegenerative disease including ALS and Alzheimer’s disease. Welcome, Dr. Cox.

Dr. Cox: Thank you very much.

Seth: It’s an honor to have you with us Dr. Cox. Thank you for making time in your busy schedule.

Dr. Cox: Of course, Seth. It’s a pleasure to be with you. Thank you for inviting me.

Seth: Well, I’m thrilled to have you with us. Lori went over a formal introduction but we don’t know from that bio how you came to study ALS. Could you share that with us?

Dr. Cox: Sure. I’m an ethnobotanist. My training is — I had to work with indigenous people to study their patterns of wellness and disease with an idea or an eye to coming up with new pharmaceutical treatments that can benefit people everywhere. I began in cancer research, moved in the 1980’s to HIV AIDS, and that was a deeply moving experience to me. HIV AIDS was a different sort of disease in the 1980s than it is now. Many people were dying and there seemed to be more than death sort of a loss of them being treated as persons and being treated with the dignity and respected that all people deserve. So I became emotionally attached to the HIV AIDS community.

For a while I think I was only one or two straight members of the AIDS Research Alliance Board. And it was a deeply emotionally moving thing to me. We discovered a new drug candidate called Prostratin in my work with indigenous people. Once that got launched down the pharmaceutical pipeline, I wanted to find another disease that I could work on that had the same sort of sense of hopelessness, maybe a sense that there hadn’t been any useful drugs discovered, maybe the possibility that a new approach that new eyes could shake loose some new ideas. I’m also very willing to work on what I call high risk research, any research that has only a very small chance of success and a high risk of failure. So I started thinking about different diseases and decided to study ALS.

So in the 1990’s, late 1990’s I quietly read everything I could find about ALS. I tried to educate myself about the illness. I decided that I would start my research by studying indigenous people who had the highest rates of ALS in the world. So with my colleagues I began very quietly in the late 1990’s and early 2000 taking expeditions to remote villages in Guam where people suffered from an ALS-like disease at about a rate of 100 times what it occurs here. One of the villagers were in about 25% of the people were dying of an ALS type disease. And so I thought perhaps if I could figure out what was going on in that village that it would give greater insights into ALS in general.

Seth: Wow. Over these years has the field progressed or have there been major milestones that have propelled your research forward?

Dr. Cox: Well yeah. The first objective was to try and understand what was happening in these villages and I think that’s a very different approach to the disease and traditional research. The only drug that’s been approved by the FDA for treatment of ALS is riluzole, also marked at Rilutek. That was approved by the FDA in 1994 and I just really didn’t see much coming out of the drug pipeline. A typical research program would be to develop a mouse model of the disease and of course in 1993 we saw the advent or 1994, the SOD1 mouse model. And then you screen a whole host of different pharmaceutical compounds against that model to see if you can improve the animal model of disease.

This was very different. We were dealing with people. It turned out there had not been prior ethnobotanical work of studies with these people although there had been a lot of neurologists through the years that had become very interested in Guam. They were all clinicians. As an ethnobotanist, I’m trained to live with the indigenous people to conform my lifestyle to their culture, to attempt to learn their language and we like to think that people tell us things that — and we gain, understand this way, that would not be gained in a clinical setting.

I think the first milestone that we gained is one that we brought the table because of my botanical training. We became very interested in a neurotoxin called BMAA. This had been isolated from the seeds of cycads. These are trees that people used the seeds to make tortillas. They make flower out of the seeds and use it to thicken stews and make dumplings.  We found two things. First of all, we were very interested that the indigenous people eat flying foxes. These are very large bats. This had not turned up in any previous studies by medical researchers. And then we also found that they have specialized roots in these trees that harbor photosynthetic bacteria called cyanobacteria.

So we cultured these roots in our laboratory.  The cyanobacteria we found produces the toxin BMAA. We then looked at museum tissues of these flying foxes and found a very strong accumulation of BMAA in the flying fox tissues. So that was really sort of the first milestone I guess would be to confirm suspicion of previous researchers that this toxin, an environmental toxin might play a role. But this research came at some cost because we realized really to our horror that cyanobacteria just don’t occur in this little island in Guam. They occur throughout the world. We got our colleagues around the world to send us laboratory samples of cyanobacteria, isolated from lakes in New Zealand, the Baltic Ocean, the streams in Bermuda, everywhere. And we found that of 30 different types we sampled I think 29 contained the toxins.

It was a bit frightening to me at the beginning to realize that people could be exposed to this toxin anywhere in the world. They wouldn’t have to live in this village in Guam. These people in Guam got a very high dose, but low dose exposures might be different elsewhere. We then were very fortunate being able to obtain autopsy tissues from Chamorro people in Guam who had died of this ALS-like disease. We found that all of them had high amounts of the toxin in their brains. This work was replicated and extended by the Miami Brain Bank, Dr. Deborah Mash who found that in 13 out of 13 ALS patient brains she studied in Miami, that all 13 had significant amounts of this toxin, BMAA. So this did not prove that BMAA exposure could trigger ALS, but  it certainly encouraged us to continue the research.

Seth: Incredible  As a side question, are there other hot spots worldwide other than Guam for  ALS?

Dr. Cox: They are indeed. Yes, there are. There is a hot spot in a remote part of Japan, called the Kii Peninsula. We have traveled there several times. We have been studying carefully the diet and lifestyle of these people. We have found BMAA in their food supplies and water supplies but are not quite ready to publish that. We have not yet confirmed BMAA in brain tissues with patients who are in Kii, so we are still working on that. There is another place in New Guinea that has a high rate of ALS. We would very much like to get there. It’s been in a bit of a military area and it’s difficult for us to get permission to go there.

The other thing that was quite interesting to me, and I was fascinate Seth, with reports of US Military personnel who had been deployed in the first Gulf War in 1992 through 1993. About ten years later when they returned, many of them started experiencing ALS and it was about two to three times the rate of soldiers that had been trained in the same way but not deployed to the gulf. Together with ALS researcher Dr. Walter Bradley who was chairman of the department of neurology at the University of Miami Medical School. We went to the gulf. I thought this might be a way of disproving our hypothesis because we typically think of cyanobacteria as the sort of the blue green scum that occurs on ponds or reservoirs during warm weather and here we’re in the desert area. But we got into Qatar, I saw an unusual soil crust, I poured my water on it. It immediately started photosynthesizing.

We since discovered that parts of the low-lying areas of the gulf, deserts are up to 87% are covered with cyanobacteria crust, which produced BMAA. So our hypothesis was that soldiers marching behind tanks going through the desert, were inhaling aerosolized cyanobacteria and getting exposed to the toxin that way. The epidemiology is quite interesting. The ground troops indeed did experience this sort of sudden spike ten years later of ALS, but so did helicopter mechanics. We puzzled, why helicopter mechanics? It turns out that the helicopters in that first deployment could only fly 24 hours or so before their engines were clogged with dust. When they land the helicopter mechanics were just covered with dust from the rotor blast and from ripping the part of the engines.

So we include US Military Personnel now in our studies and we have been very interested in the possibility that people could be exposed to the toxin either by inhaling dust from cyanobacteria in the deserts or by inhaling aerosolized cyanobacterially contaminated water from lakes and reservoirs or by eating shellfish that had been contaminated with BMAA. So we have been working very carefully trying to figure out what are the most likely exposure roots of people with these toxins.

The picture that’s emerging Seth is that we believe that at least some points of ALS result from gene environment interactions, their interaction between having a vulnerable genotype and then having exposure to this toxin that serves as trigger. The BMAA hypothesis is that the genotype is like a gun and the environmental toxin is the trigger. So our focus, which is quite different from mainstream ALS research, is to try to find drugs that can block that trigger. That’s led to our current investigations of the amino acid L-serine.  

Seth: Thank you for that answer. We want to dig further into the unique approach of the Center for Ethnomedicine.  But first we’ll pause.  Our listeners are listening both by phone and over the computer. For those who have a question for Dr. Cox I’ll have Lori tell you how to ask.

Lori: To ask a question, dial 516-590-0362 and press 1 to indicate that you have a question and you will be on hold while you listen.

Seth: Thank you, Lori. Now as you mentioned you’re a bit different in your efforts from mainstream research. As Lori mentioned you are located not at a university, but we know you are associated with other researchers around the world.  Could you tell us a little more about how the center for ethnomedicine works?

Dr. Cox: Sure. Unfortunately, we have just rebranded ourselves. We call ourselves now the Brain Chemistry Labs because people were struggling trying to figure out what on Earth ethnomedicine is. So we’re the Brain Chemistry Labs at the Institute for Ethnomedicine in Jackson Hole, Wyoming. What I did, when I started realizing that we had a lot of different interesting aspects of the story that was immerging I felt that we needed to have an interdisciplinary global group of researchers all working together. I felt that no single discipline could succeed in trying to discover a new ALS drug.

And so I have gone around the world to various researchers in different areas including chemistry, neurology, synthetic chemistry, oceanography — I cherry picked the top minds in the world. So I said you know, you’re doing a wonderful work now. I asked them would you please stop and come join with me? I’m trying to find a cure for ALS. I Tell a little bit about our research to the person, and they have always agreed. So we have 50 researchers now around the world in 28 different universities or government labs. I think we’ve got 12 or 13 countries represented. Everybody checks their egos at the door because you may be good in neurology but not know a whole lot about oceanography. It’s been sort of fun to see researchers share and help each other.

One of my frustrations with drug research in general is that in a typical pharmaceutical model, the scientists are siloed up. They’re not sharing information. I have worked with now five or six pharmaceutical firms during my career. They’re great research organizations but you have to sign a pile of confidentiality agreements about six inches thick. And I don’t think that’s a good way to find drugs. It’s to sequester information. Furthermore, I have been concerned about using the for-profit model as a mechanism of drug discovery. A lot of people say to me wow, given your result, why don’t you form a biotech? And the answer is well because I care more about patients than profits. I don’t really don’t want to worry about some costs. If we find something that doesn’t work, we just drop it that day, we don’t pursue it. I never want to worry about a shareholder. I worry about the patients. That’s our whole goal here.

The 50 of us are communicating all the time. I mean this morning I was talking to about 12 researchers ranging from Miami to San Francisco and Phoenix. We share experiments. We get together at least once a year, all of us for a no-holds conference and basically we just have one single wish which is to find new therapies for ALS. We basically created a virtual pharmaceutical firm without investing the brick and mortar and all the cost of marketing. We have a faculty of 50 on our little virtual pharmaceutical firm and it’s been a terrific experience for all of us.

Seth: Wonderful. We love to see new ways of attacking this problem. Now, does this mean that you do not pursue FDA approved trials or something different.

Dr. Cox: Well that’s been the great thing is that the FDA has been fabulous with us. If we discover something, our goal is to go immediately as soon as possible to human clinical trials because that seems to me to be the major stumbling block in translating new research discoveries at the lab bench to this patient bedside. So we have now — let’s see, we’ve had two different trials approved by the FDA. The first one took us five to six weeks. The second one took us four days which I think was a record. We’re just finishing that trial up and now we’re moving towards a phase 2. I think part of this is because the FDA contrary to some rumor, not the bad guys. They just want to protect people and patients particularly from hokey stuff and things that can hurt your health or damage them. We give the FDA the information they need.

Our clinical workers and researchers are topnotch. Again our clinicians are really four centers now, Dr. Walter Bradley at the Miller School of Medicine University of Miami, Dr. Robert Miller the Forbes Norris ALS MND Clinic in San Francisco, Dr. Elijah Stommel Department of Neurology in Dartmouth Medical School and Dr. Todd Levine, Dr. David Saperstein at Phoenix Neurological Associates. These guys are all really well regarded in the research community, well-regarded by the FDA and so — no, we are pursuing and have been granted licenses by the FDA to conduct human clinical trials. It’s just that our trials are coming from a very different place. They’re not coming from mice models. They’re coming from studies of indigenous people. So far, we’re pretty excited about the progress we have made.

Seth: Thank you. We will paue again to tell our listeners how to ask a question.

Lori: The phone number to call in is 516-590-0362 and push 1 on your phone so we know you have a question.

Seth: Thank you. So Dr. Cox, once you formulated the BMAA theory, how do you proceed to test that theory?

Dr. Cox: Well maybe I can give you a little bit of sense of our first FDA approval of L-serine to test in human clinical trials. We discovered with our colleagues in Australia Dr. Rachael Dunlop and Dr. Ken Rodgers that BMAA can be mistaken by our cell machinary as  a normal amino acid and insert itself in the proteins and cause them to misfold, untangle, to aggregate. In fact, ALS is considered a tangle disease along with Alzheimer’s disease, Parkinson’s, Supranuclear Palsy, Pick’s Disease and a half dozen others. And we got very interested in how this tangling is caused. We discovered together with our Australian colleagues that by increasing the amount of one of the normal dietary amino acids, L-serine in cell culture that we could actually stop neuronal cells from dying and these proteins from misfolding.

We then contacted Dr. Joy Goto who is chair of the Chemistry Department at Cal State Fullerton. Dr. Goto although she’s a chemist is an expert on studying fruit fly responses to toxic insult. And so she quickly confirmed these in vitro results with a fruit fly model. When exposed to BMAA within three days, fruit flies start having inability to fly, gait paralysis. When we added L-serine to the fruit fly chow, they didn’t have that problem and we found that we could even – rescue some of them up to 24 hours after hitting them with BMAA.  So armed with that in vitro data and the in vivo fruit fly data, we went immediately to the FDA.

Now we sort of do everything backwards at our laboratory because the typical academic program is first of all, you get the idea, then you write a grant and you wait a year or two to get your grant approved and then you do the research and then after a year, you publish and then after you publish maybe you somehow find some way to work with a clinical researcher and live in the clinic. Here, we do everything backwards. We immediately took these results straight to the FDA, said please approve our request to begin human clinical trials, FDA approved within a week. We brought in our team of clinical researchers Dr. Todd Levine and Dr. David Saperstein at Phoenix Neurological Associates in Arizona and then Dr. Robert Miller and his team at the Forbes Norris ALS MND Clinic.

We begin dosing patients with L-serine in different doses. As you know, a phase 1 trial is basically to confirm that the drug does not harm patients or worsen their disease. We have just finished this trial now. We are working on the publication. The good news is that it really doesn’t appear to us that they’re really serious or significant complications to patients from taking orally L-serine and we’re now preparing a phase 2 trial. We’re trying to raise 1.5 million dollars to do a 60-patient trial to see if L-serine can slow the progression of ALS disease symptoms. And we’re all pretty excited. I mean we don’t — we really won’t know until it’s been proven in a clinical that it works. But that led us to do some interesting primate trials in the island of Saint Kitts.

Seth: Wow. Now is L-serine an approved drug or is it a supplement? Tell us more about L-serine.

Dr. Cox: Well what we decided to do is I wanted to see — I mean I have some reservations about the mouse models and rodent models. I mean my hat is off to all the great people who work on them. So this is no way a critic of their work. But where our focus is on moving so quickly to human clinical trials, we wanted something that was closer to human beings to get a heads up on how L-serine might work. So we started studying vervets on the island of Saint Kitts. Saint Kitts is a Caribbean Island. Vervets were introduced there from Africa maybe 100 years ago. They have gone wild. They don’t belong in the island. There is 30 or 40,000 and so there is a couple of research colonies on Saint Kitts. These are very nice places where the animals are housed in groups and big enclosures. It really feels more like a zoo than a research facility. The animals are happy. The wild vervets try to break in there.

We went through an institutional review board, raised the funds from our board of trustees in the John and Joseph P. Lewis Foundation because it’s expensive to do primate trials. So we started supplementing, feeding these vervets on an extended period. What we noticed in the village, and this is work done by Ralph Garruto and others at NIH, if these villagers left these villages in Guam had such a high rate of this ALS-like disease that they could move to California and be there for 15 or 20 years and then come down with the paralysis and muscle denervation characteristics of ALS, meaning that there is a long latency to this disease. So what we tried to do is compress into 140 days about 15 to 20 years of Chamorro exposure to the toxin.

Each day the animals would be handed. We just give him a banana. Inside the banana would be a place to powder test substance. It’d be either BMAA or rice flour for placebo or BMAA plus Serine and then we had a very low dose of BMAA. We did this for 140 days. We are astonished by the results, replicated the study and we just published that at the end of January in the Proceedings of the Royal Society of London, series B. We’re pretty excited about the publication. What we found was that after 140 days of chronic dietary exposure to BMAA that these animals started developing neuropathology that’s strikingly similar to what the Chamorro people have in the villages. We also found that when we added L-serine to their diet that that significantly reduced the amount this neuropathology.

Armed with that and our findings from the phase 1 trial that it’s safe for ALS patients to take Serine in oral doses up to 30 grams a day, we now prepared the protocols for a phase 2 clinical trial on L-serine to determine if it can actually slow disease progression in ALS patients. There have been a few anecdotal reports of patients that claim that it’s helped them or it slowed their progression but we really won’t know until we see if it works under a really rigorous clinical setting. And that’s what we have designed. We’re hopeful that as soon as we can raise the funds that we can get permission from the FDA and launch this trial. And I have to push a cautionary note here which is that we totally support the FDA process and it’s really important for us to know if it works or not in the clinical setting before we get everybody all excited because at this point don’t know.

So please I’m not encouraging patients to add L-serine or go out and buy anything else to take. What I’m saying is that we really want to find out as soon as possible if this shows a benefit. And if it does then of course, we’ll be pushing the FDA for preliminary approval. Then if it doesn’t then we’ll drop this and move on to the next drug candidates. That’s the way our research works and it really doesn’t matter if we can cure every fruit fly or mouse or monkey in the world unless it works in the clinic. Again our focus has been to accelerate human clinical trials as quickly as possible.

Seth: Do you recall the numbers from your primate research?  Were all of the vervets dosed with BMAA or would those — did they develop symptoms?

Dr. Cox: Well that’s a really good question Seth and the answer is none of the animals developed symptoms. What we found was neuropathology that would be preclinical that would be consistent with Chamorros who will get sick but haven’t done so already. So our findings were based on neuropathology and not signs in terms of behavior.  What sort of astonished us I guess was that all of the BMAA fed animals developed neuropathology but those that we had supplemented their diet with L-serine had a 50% to 80% reduction of neuropathology. So we all feel very strongly that this is something we need to follow-up quickly on now to see if we can see if it works in the clinical and human beings are not and we are ready to go as soon as we can raise the 1.5 million dollars.

Seth: Thank you for that clarification. At this point, we will pause to take the question of an online listener.

Dr. Cox: Thank you.

Lori: We have a question from a caller ending in 6431. Go ahead. You’re on the air with Dr. Cox.

Caller: Thank you so much. You can hear me?

Dr. Cox: Yes, I can. Thank you.

Caller: Okay. Dr. Cox, thank you so much. It is so exciting to hear about your work as a person who has an ALS relative, I just can’t thank you enough for your collaboration across the globe with people concerned not about the bottom line profit but about helping people. Thank you. Now, my question is, does ALS manifest itself the same way, did it in Guam as it has in other places as it does here in the US? Is it the same nature?

Dr. Cox: Oh, that’s a really good question. The answer is the Guam disease is somewhat unique. What happened was in the aftermath World War 2, when the United States retook Guam from the Japanese who controlled it, US Army physicians started noticing these patients with ALS-like symptoms and started counting them up and realized to their horror that is 50 to 100 times the rate of ALS elsewhere. But the disease has some distinct differences in Guam and elsewhere. Sometimes the patients in Guam show symptoms of Alzheimer’s disease. Sometimes the patient shows symptoms of Parkinson’s. Some unfortunate individuals have symptoms of all three.

Clinically it was different and neuropathologically is different too because the Chamorro people show in their brain tissues those who have the disease brain plaques and tangles that are quite characteristic of Alzheimer’s disease but which we typically don’t see in abundance in ALS patients. And what we reported in our paper in the Royal Society of London in January was that we had found these brain tangles and plaques in the brains of these vervets that had been chronically exposed to through their diet to BMAA. We’re still continuing work with the Miami Brain Bank looking now very carefully for Neuropathology consistent with ALS and we don’t know yet but we are excited to find out if that occurred.

Caller: Thank you. My final question would be you say that you’re in need of funding to go to the next step. Will this happen by huge grants or is there any way individuals can participate in this? What will be helpful to you?

Dr. Cox: Right. Well thank you very much. And again Seth let me say that my purpose here in participating this call is not to raise funds. Look we are in a not for profit organization. And so when ALS patients come and see us or talk to us, I tell them we look forward for you. That’s it. There is nobody else. I mean I think there is very few people in the world who wake up every morning, thinking about ALS other than ALS patients and families, and we’re there. So the message really here Seth for the listeners is one of hope that there is a group of people in Wyoming that are augmented by 50 people around the world. We are all over from a variety of disciplines and we are very, very determined to keep pushing forward.

That said, as a non-profit organization, we’re supported about 40% of our funding comes from our board of directors. None of whom have ALS or ALS in their families but they are just public spirited people. About 20% comes from research foundations and a remainder from well meaning individuals. Everybody that donates a dollar to us, I sent him a letter every month, to keep them up on the research. But so far, we have been very fortunate, we have a fairly small budget. We have been spending about 1-1/2 million dollars a year plus whatever it costs for the clinical trials. But at this point, we need to do a clinical trial. I have been looking for 2.5 million for 120 patients. None of those funds would be used by us. It all goes to cover hospital cost and clinical cost and trial.

That’s a bit daunting. So we have reduced it now to 65 patients to 1.5 million dollars and as soon as we can get these funds, we’d be able to go forward and I’m quite hopeful that we can find this from private sources. Our research is so different from mainstream ALS research. Most of the mainstream researchers have been studying genetic determents of ALS and as you and your listeners know about 8 to 10% of ALS patients have a family history and about half of those have an identified mutation, like SOD1, or TP43, or FUS.  

Our focus is on sporadic cases where there is no family history but we are outside not only of the mainstream research. We’re outside of mainstream funding. And so we have been raising the funds on our own and it’s been just a wonderful thing. There is a family and Logan Utah. Lee Badger was a beloved member of the Logan Utah Community who owned Lees Marketplace, the chain of grocery stores.  When he passed away from ALS his family decided to fight it. So they started a golf tournament in Logan Utah and I think that’ll be June 3rd this year and everybody comes up and has a good time in that golf tournament in Logan called the ALS Challenge has been supporting our research now for four or five years. And there is just other people that do wonderful things to try this out.

But again Seth, it was not to try to raise money through this interview but just to let people first of all that there is hope, secondly that there’s people that are thinking outside the box and approaching this for a very different angle and third that we have made some success now. We have really seen some real progress particularly with the primate study and particularly with the phase 1 clinical study that’s pushing us forward now to do a phase 2 study. Once we get the funding, I’m quite hopefully that we can finish that study within 12 months and we’ll know yes or no can L-serine help slow the loss of muscle and neurons experienced by ALS people.

My personal goal was to — I don’t know if I can cure ALS but I think we got a shot at slowing it down buying patients more time with their family and their loved ones and buying more time for where they can stay functional and my real dream would be to change the landscape of ALS so it can be managed as a chronic disease much like multiple sclerosis is already. I think that’s possible. I think that’s within our grasp and I’m optimistic and I want to pursue every avenue I can to see if we can achieve that.  And if we fail, well we fail. But it’s a great cause and one that we’re fully invested in.

Seth: Thank you. Thank you, caller for your question. Now Dr. Cox, many of our listeners are unable to speak or call in over the phone. We have a number of online questions that Lori will read.

Lori: Thanks. We have a series of three questions from a listener that kind of go together. What does the L-serine treatment look like in humans? What would the dose would be? What are the side effects that it may have and how can an ALS diagnosee get involved in your clinical trials?

Dr. Cox: Well let me start with the first one. L-serine is a common amino acid in our diet. It’s rich in soybeans and soy products like edamame. It’s rich in sweet potatoes and pork and eggs, bacon. So we’re already getting on average about 3-1/2 grams of L-serine from all forms of our diet. That’d be average for Americans. In our phase 1 trial have orally dosed patients up to 30 grams per day and doing it twice a day and what we’re still working on the manuscript. We want to publish it and of course take to a peer review. But the preliminary result suggests that patients tolerate that well. Side effects that we have noticed in patients include bloating, nausea in a couple of patients.

I cannot recommend a dosage because I don’t know and furthermore it’s not been approved by the FDA. So again my advice is to just stay tight until we can find out if it’s working or not because I don’t want to do anything to suggest any practice that people would adopt that has no efficacy. For the phase 2 trial, if we can get the funding quickly and get it approved quickly and I’m optimistic that maybe we can do both of these things. The trial will occur at a couple of centers. I think it’ll occur at Dartmouth Medical School, occur at the Forbes Norris ALS Clinic in San Francisco and occur at Phoenix Neurological Associates and a couple of others.

Basically my best advice is to just stay in close touch with your physician and as these opportunities become available, I’m sure your physician will let you know. The other place you can look for news is we have a website ethnomedicine.org which is E-T-H-N-O- medicine.org. People are happy to look there. We always are delighted to welcome ALS patients at our laboratory in Jackson Hole, we’re just off at Town Square opposite the elementary school. Although we can’t advise people with medical conditions because we’re all PhDs, we are not MDs, we delight in sharing our research with patients. We have a number come up and see us and we’re not in a position to diagnose or prescribe but we do have this really heavy hitter neurologists in Dr. Walter Bradley.  He’s sort of like Yoda in terms of the ALS Community. I mean he has been awarded as the top ALS clinician researcher. Dr. Robert Miller in San Francisco, it’s the same thing. We’re like having Yoda and Obi-Wan Kenobi on the team here. Dr. Miller’s clinic in San Francisco is so fabulous.  What has really impressed me is the deep respect and dignity they accord to patients. So we have got the right team. We have got an unusual approach and unusual idea but we have some promising preliminary results and our goal is to see if we can — see if they work in the clinic or not and we aim to do so in a very rapid fashion.

Seth: Wonderful. In time we should not stay away from bacon and eggs for breakfast, correct?

Dr. Cox: Well, any guilt that you feel on eating bacon and eggs, you are hereby resolved. In my own life, I have changed my diet. I’m eating a lot more edamame. I buy little packets that I throw in the microwave from the frozen vegetable section and I eat them for breakfast and I eat them for lunch. So I’m jacking up my own L-serine content and again if it doesn’t pan out in the clinic, well so be it. But it’ll be so wonderful if it works because this is a relatively non-toxic treatment and we just love to know if it can help people or not.

Seth: Excellent. Thank you for that removal of my guilt. Now we would like to talk briefly about what other ways will your reserach progress? Is it solely through the trial?

Dr. Cox: Well I have pretty deep feelings about ALS and we put pictures of patients up in our laboratory. My team is so amazing.  We went out canoeing; we took one day off one year in the afternoon,  and went canoeing on the Snake River.  Then we brought the canoes back and I asked Dr. James Metcalf, my key cyanobacterial specialist “Can I take you back to your home?” He said, “Well no. Could you drop me at the lab?” I said “Why? It’s 10 PM.” And he said, “Well I still think I have time to make one more experiment.” So that’s the sort of spirit here is that there is one more experiment.

That being said, I can’t speak for patients and their families but it seems to me that if I were the patient I would take heart in people trying all sorts of different approaches to ALS. The current approach, again the last drug for ALS came out in 1994. I mean that’s what, 22 years ago. That’s just outrageous. I’m really frustrated by this. I think there should be as many different approaches as possible, all carefully screened by the FDA and under rigorous clinical conditions and hope that one of those would yield a new drug, a new treatment that could be a benefit for patients. And so I would like to see obviously more approaches rather than narrower and more highly focused approaches.

Again, I think everybody in the ALS Community is working very hard and there has been some spectacular advances made in understanding the genetic basis of familial ALS. But as far as I’m aware, our consortium, we’re the only groups working on environmental triggers and yet the teams we have, I mean William Camu, neurology at University of Montpellier, Christian Conradie at Karolinska Institute. I think we have got a shot. I don’t know how bit a shot it is but we have got a chance and we’re going to take that shot and the way to take the shot is to complete a phase 2 clinical trial to see if it’s efficacious in slowing progression of disease symptoms in ALS patients.

Seth: Excellent. We have one final question for you. But before we go I’m going to ask that Lori tell our listeners about our next episode.

Lori: Our next episode for ALS Crowd Radio will be Wednesday May 4th at 11 AM Mountain Daylight time with Dr. Richard Bedlack speaking about ALS Reversal.

Seth: Thank you, Lori. Dr. Cox, we’ve covered a lot of ground in this hour and how people can get involved in your research. But from your perspective what is the greatest opportunity in ALS for people who care to get involved?

Dr. Cox: You know it’s such an interesting question. One thing I’ve really felt is that it’s a real gift for me to have been able to meet such wonderful patients. There is something special about ALS patients, not just that they’re facing a desperately devastating disease but they tend to be very nice people and what I have noticed is that the patients that get involved in clinical trials do better even if the drug doesn’t work and that’s because they’re under observation all the time by a physician.

People that are very proactive in fighting it seem to do better and again, I would encourage your listeners to go on to our website at ethnomedicine.org. There is a film, a short film clip there. They can get an idea of our research and research papers and I guess what I really want to say is thank you because we have received so many encouraging notes and messages from ALS patients and their families and it’s been a very deeply moving experience for me to get involved in this community and I just — my prayer is that something that we do in Wyoming with our colleagues will turn into benefit for ALS patients. If that happens, we’d be delighted.

Seth: Thank you. Thank you for your time, Dr. Cox. It’s an honor to speak with you and please relay to your staff our gratitude for their work and sacrifice on our behalf.

Dr. Cox: I’d be pleased to do that, Seth. Thank you.

Seth: All right, thank you, listeners. This has been a great episode. Please tune in and join the next episode. Thank you again to Dr. Paul Cox of Jackson Hole, Wyoming.

2 replies
  1. Erik Johnson
    Erik Johnson says:

    I am a survivor of this incident, which led to the creation of “Chronic Fatigue Syndrome”
    Despite Dr Snyderman’s assertion that there were no warnings or clues, we were actually in the middle of an algal bloom. Which scared people to death.
    I felt a burning sensation all over Incline Village. Worse, closer to the lower part of town.
    I went to the beach to try and get some fresh air. There was a horrid neon green substance that looked like fluorescent spray paint. I told CFS researchers about it, but they ignore me. They want’ the Tahoe Mystery Illness to be a virus.
    I was the only one of the original CFS cohort who saw the neon green stuff on the beach, although there are a few who remember the burning sensation in various places on the beach.
    The few CFS researchers who would even speak to me said even if this were true, there is no way to find out, “so it doesn’t matter”

    http://www.youtube.com/watch?v=AW0x9_Q8qbo&feature=related

    Reply
  2. Louis Puig
    Louis Puig says:

    I just read various stories and studies on how BMAA toxins in blue green algae attack humans and causes motor neuron diseases such as Alzheimer’s and Parkinson’s. Obviously I am quite concerned since I have been on E3LIVE blue green algae for years. I am curious as to what the chances are that E3LIVE contains BMAA. Millions are taking this product and similar products such spirulina. I wonder just how safe these products are and if they are not then someone should be warning us. I have tried without luck to get through to Dr Cox, Dr Dunlop, Dr Bradley and Dr Mash to ask them these question. Please relay this message to Dr Cox as this could prevent motor neuron disease in many people. Let me know if you have any luck at louispuig@aol.com. Thanks.

    Reply

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