Lewy Body Roller Coaster
Lewy Body Roller Coaster
Part 3 Information About the Syn-one Skin Test
Welcome back for part three of our interview with
Dr. Todd Levine from CND LifeSciences to share with us all information about the new syn-one skin test that can help in diagnosing LBD.
Our good friend Wendy Cogan joined us to help ask the right questions so we get a better understanding of this new test.
This is a three part recording because our interview was well over an hour and a half but we had lots of questions to ask the doctor.
Enjoy part three
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https://cndlifesciences.com/
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Hello and welcome to our podcast about living on the Lewy Body Roller Coaster a podcast for Lewy Body Dementia patients and their families. Presented by Lewy Body patients and their families.
Speaker 2:You will hear firsthand the ups and downs and twists and turns of Lewy Body Dementia From families directly affected. We'll share our support and experiences on all things Lewy Body.
Speaker 1:We're your hosts, Linda and Curry. I have a loved one with Lewy Body Dementia.
Speaker 2:And I am living with Lewy Body Dementia.
Speaker 1:Let's get started. Welcome back podcast family.
Speaker 2:Please welcome back to the podcast Dr Ted Levine and also a guest helper, wendy Cogan, whose husband has Lewy body dementia.
Speaker 1:Dr Levine, I think you mentioned earlier about the NIH. Can you update us on the progress of a synuclein-1 study funded by the NIH and when will the findings be available? Because we noticed that it's being offered in 20 by 25 clinical sites and I guess the most important question is are you still accepting people in the study and how can our listeners become a part of it?
Speaker 3:Yep. So the study was designed to be the largest kind of prospective study to say does the skin biopsy help? Now what we've done in the study is to say we're taking people with the force of nucleonopathy, so not REM behavior disorder, so Parkinson's, msa, dlb and pure autonomic failure who are clinically definite, so the ones that the doctor says I'm as sure, sure, sure as I can be, because we're not going to obviously do autopsies, so short of autopsies, it has to be the doctor going. I'm really, really, really sure that that's what this patient has. And then we're doing the skin biopsies on them. So previous studies, our work, the Italians published last year, you know big studies are 50, 60 patients. This will be 500 patients. So it should be the definitive word on how, what is the sensitivity and the specificity of the SYN1 test. We hope to complete by December enrollment and then, you know, we probably have the data by this time next year. So, figure 12 months, we should have all the data. The other thing that we're doing in that study, as we have talked about, I think, before, is that because myself and Dr Gibbons, who are the blinded pathologists, so we won't really know what the patient has, we're trying to say can what we see help say this is more likely Parkinson's or more likely DLB or more likely MSA? So we're going to do all of that. So we should have that within a year, wow. And then, if people want to participate.
Speaker 3:So we had, as I said, the four different diseases. Some of those diseases have closed already. So, for example, parkinson's disease, we filled up very quickly, as you can imagine, but we are still looking for DLB patients. So I know the last half of this year we would welcome anyone to do that. The sites are on our website. I think there's, as you said, 25, maybe 28 at this point, and you can also go to clinicaltrialsgov, look for our study and then you could see which centers are enrolling and then hopefully there's a center that's near you. So someone who wanted to participate would have to go to the doctor at that center. It's about a three-hour visit to do all the clinical information, do the biopsy. It's just a single visit and that's it. So we would definitely welcome DLB folks.
Speaker 1:Now, are you looking for people just with MCI, or are you looking for people already diagnosed with LBD?
Speaker 3:So in the SYN1 study we want people that are already diagnosed and again the ones that the doctor says this is textbook case, no questions asked kind of case. This is, you know, textbook case, no questions asked kind of case. We just were awarded another grant by the NIH to look at the MCI folks. So this was we're going to compare mild cognitive impairment of the Lewy body type to mild cognitive impairment of the Alzheimer's type. We have not yet enrolled all of those sites. We probably will have about 10 sites in that study. It'll be a little smaller study and they'll probably be. Some of them will be enrolling by the fall. So definitely just keep watching our website or clinicaltrialsgov, and I would definitely like to find those people.
Speaker 1:Yeah, he's got a question. Do you see his pen?
Speaker 2:Yeah, Doctor, let me ask you a question. Just reiterate, if you will how far in advance do you think that your can recognize illnesses like Lewy body dementia?
Speaker 3:Yeah, it's a great question, so we don't really know. What I can tell you is that our best data is that REM behavior disorder develops five or 10 years before the other conditions. We can see the abnormal SYN1 test in REM behavior disorder about 85% of the time in REM behavior disorder about 85% of the time. So that would mean in 85% of the patients we can probably see the protein starting to accumulate five to 10 years before the full clinical symptoms begin. It may be longer, but that's the best sort of comparison.
Speaker 3:Because of that, there is a group of very smart sleep doctors neurologists mostly across the country that have formed a group called NAPS, which is the best name for sleep doctors to call. Their group is NAPS. I love it. I'm very jealous that they came up with that name, but it stands for North American Prodromal Synucleinopathy Group, so they are looking for the prodromal people, right, and so this is where I get very excited.
Speaker 3:I love the question because it's one thing if we say, okay, I can diagnose Lewy body much more definitively with this test, but we know by the time that that's been diagnosed the protein's been accumulating 5, 10, 15, 20 years, and so the ability to get that protein out of the brain and to save neurons is going to be a challenge, right. I mean that's going to be tough. I think we'll get there eventually, but that's going to be tough. On the other hand, if you could detect that 10 years before and say this protein is starting to accumulate in this person, now let's give them that same drug and slow it down by 20 or 30% Now maybe they don't get the disease till they're 90 as opposed to 60. So that whole starting to diagnose this much earlier and treat much earlier is actually starting to become a reality because we can see it before the person has all the symptoms of the brain damage that occurs from the protein accumulating.
Speaker 1:Thank you. Yeah, that's big because we I can't even tell you how many people have come on the podcast and people who come into the support groups. Kari was a rare one. He got a quicker diagnosis but the wrong diagnosis, like Wendy said, and sometimes up to five years to get the proper diagnosis, and that's a lot of time that they could have been living a better quality life with the right meds. And one of the big things is because they're not diagnosed, they get meds that make. One of the big things is because they're not diagnosed, they get meds that make the Lewy body worse. So I'm very excited that this is taking place and that you are all working so hard towards this disease and I just pray there's a cure someday in our lifetime, but I guess this is a start. So, wendy, you want to jump down to your next question, because he already answered mine.
Speaker 4:Yeah, yeah, and actually I just have. When I was listening to the discussion, a couple things popped into my mind too was how important it is to understand the pathology so that you are using the right type of medicines and you getting into the right type of clinical trials, and also a point that was made earlier about the difference between pathology versus a biomarker. So my husband had the positive DAT scan and at the time, um, I thought that meant you know that, uh, synucleinopathy type of thing like Parkinson's or MSA or Lewy body. But what I didn't realize at the time is that it can also be positive for cortical basal syndrome, which is the disease that, um, they suspected my husband had. And then ultimately, of course, the skin biopsy showed that he has at least the alpha-synuclein pathology.
Speaker 4:But I do think it's important to mention that probably a lot of dementias are mixed and maybe, you know, at the time of the autopsy or death, the mixed dementia has become pretty much more likely than just a single dementia. And I do wonder at times if maybe my husband has two type of dementias. We know that he doesn't have the Alzheimer's because we can tell by cerebral spinal fluid and scans, but we can't tell yet other diseases that are caused by things like four-hour tau, and so it's possible that maybe my husband has the four-hour tau too. But back to understanding the pathology and why it's so important is that this Aricep really works well for Lewy body dementia patients. It really helps with cognition. But sometimes the doctors say if you've got the wrong disease and the person actually has cortical basal syndrome and you give them something like Aricep, it can make psychiatric conditions worse. So that's why I think it's really important to know the pathology and the disease so you can treat it properly.
Speaker 1:Yeah.
Speaker 3:Sorry, I was just gonna sort of add to that. I agree completely and I think in Lewy body it's unbelievably important to think about the medications we choose, because People with Lewy body dementia can have behavioral problems. They can be hospitalized or seen by psychiatrists and given medications that will make their disease much worse. If you don't know that it's Lewy body More so than the other conditions Well, maybe Parkinson's too, but usually it's a little more clear. But with behavioral problems, really understanding what medicines are safe for a Lewy body patient to take and not is critical, Because I mean, I've seen, unfortunately, circumstances where I think a patient's death was hastened with Lewy body dementia because they were given the wrong symptomatic medication. So it is critical.
Speaker 4:Yeah, yeah, and that was definitely what happened to my husband. He was on lithium and he was doing okay, but it wasn't impacting his cognition and made him appear like he was having tremors. And then they put him on a urinary medicine that caused his levels of lithium to go up and he went into the full blown delirium, and so it took a while to get that all figured out and sorted out, but he's able to handle like the Aricep has helped tremendously. And so you got to experiment and you also have to know the disease, what you're dealing with. So that's a really important point.
Speaker 4:I did notice and I think you've addressed this to some degree, but I did hear that there's a Swiss biomarker or Swiss biotech company that, during the March 2022 International Conference on Alzheimer's and Parkinson's Disease, announced a potential new pet tracer that can differentiate MSA from Parkinson's disease and Lewy body dementia in living patients. And initially I was going to ask you if you guys were evolving to be able to tell the differences between, like Parkinson's and Lewy body and MSA. But from what you explained earlier, this NIH study might help you actually get there. You might actually come up with a conclusion that says, hey, we can differentiate these four or five different diseases. So that's wonderful.
Speaker 4:So the other thing is we talk about clinical trials. Um, one thing that's really important when you're looking at the pathology or a biomarker is you've got to be able to tell if a certain intervention or drug is actually working and you've got to be able to have a biomarker to measure that and to show improvement. And right now, as you say, it's more of kind of a yes, no, you know whether they have the piece in or whether they don't. This that maybe you can, but do you think you'll be able to evolve your test to be able to tell disease progression or severity so that it can be ultimately used in clinical trials?
Speaker 3:Yeah, so we're using it in clinical trials in just that way now. So we're working with three different pharmaceutical companies to do pre and post biopsies and to see whether or not the levels change. Now what we know is that if you follow at least Parkinson's patients, you see about a 7% increase in the amount of sunuclein per year, in the amount of synuclein per year. So the hope would be then that once we have a drug that decreases it, that we would be able to see that decrease or at least that stabilization over time. So far those trials are still ongoing. So far none of the drugs have been able to accomplish that yet. But the hope would be that once there's a drug that can reduce the synuclein, that the SYN1 test would be able to look that yet. But the hope would be that once there's a drug that can reduce the synuclein that the SYN1 test would be able to look at that.
Speaker 1:Yeah, this is. I'm riveted. That's why I'm just riveted listening to all this. So, wendy, thank you for helping us dig deeper into this, but I, for time's sake, because we do a Zoom at 1030 on Mondays central time, so it's 15 minutes and I know I've got to give my buddy Corey a rest.
Speaker 4:Do you?
Speaker 1:want me to ask my last question, if you go down to page 10, because as a woman. I'm asking this as a woman because the women in our groups say how hard it is, that they seem to have a harder time to get diagnosed. So has Sin 1 development tests been based on male symptoms? I guess that's what I'm asking. In your study, is it equal amount of male and female? Because women with LBD seem to have less REM sleep behavior issues, could the test be missing some differences in females, like hormones or other variables? So I'm asking this for all the women out there who we have, several that are struggling to get diagnosed and and it and it's, it's bad. It's bad where they say to them like, oh, you're just going through menopause or it's just a woman thing. So I'm asking this for all the women out there trying to yeah.
Speaker 3:So it's a great, really, really complex question, so I'll try to answer it a few different ways. So first is, we don't see any sex difference in the pathology and I have to get you the exact numbers. But if you look at the sex of the people that have gotten the test done, there's not a huge difference that we've seen so far. So if you look at the sex of the people that have gotten the test done, there's not a huge difference that we've seen so far. So I don't think the test would be affected. Now, could it be affected by things like hormones and other things? I suppose it could, but so far we haven't really seen that. Then the second part of the question is why is it harder for women to get diagnosed? So that's really complicated, but I'll start by giving just some facts. We know, for example, that women who have heart attacks are much less likely to complain of chest pain. That's been well described for 70, 100 years now. We know that women are less likely to get seen for cognitive complaints at the same time as men. Now one argument is that's because if people have dementia, it's usually the caregiver or the spouse that brings that person in. It's very rare for a person to come in and say I'm becoming forgetful. It's not impossible, but it's usually the spouse that says they're becoming forgetful. And one could argue that the female spouse is just more observant than the male spouse and therefore men are brought in much sooner than women. My parents are both in their 90s and I would say that applies to them as well who both have some cognitive issues. So that is one issue. It's sort of an observer bias, right? So if the people closest to them have to observe the cognitive loss, that could be a problem. The second would be the patient bias, which is like the women with the heart attack story. Women just don't complain of it as often and that may be part of the story of it as often, and that may be part of the story you were alluding to. What I hope isn't the case, but which is a third possibility, which is that women who present complaining of cognitive problems may be told more often that it is something other than cognitive problems, that it is their depression, that it is the divorce they're going through, the death of their whatever, and that men don't seem to get that response from doctors quite as much. I hope that's not the case. But it's probably some combination of all of those things that lead to that.
Speaker 3:Sometimes in our lab we talk about the moonshot, right? So what would happen with our lab if we were JFK and we were trying to get to the moon? You know, kurt, your point. My moon shot for what we're starting to do here, and we'll probably be long after I'm gone, would be kind of like the colonoscopy. So imagine, for example, we all at 50, we get colonoscopies, we get mammograms because we're screening for cancer, right? Imagine you could do one skin biopsy at 50 and screen for synuclein and tau and TDP43 and all of those proteins that are going to build up in 20 or 30 percent of the population as they get older. And then imagine that we've got drugs that now can block the accumulation of those proteins and you're starting them long before you're symptomatic. That's again my moonshot.
Speaker 3:That's how you cure lewy body and alzheimer's. You can't cure it once they're demented. It's just, it's just going to be too hard. Um, you've got to stop it from ever happening, and so to stop it from happening. You've got to stop it from ever happening, and so to stop it from happening, you've got to identify it, then get the drugs and then treat the people. So some of this may get resolved over time because we're going to start screening for all of these neurodegenerative diseases in a way that we have medications for. And that's sort of my you know, that'll be my dream.
Speaker 1:Keep dreaming. Reach for the stars as teachers always say Wendy has one.
Speaker 2:That was very good. Go ahead.
Speaker 1:Yeah, wendy has one quick question and then we're going to wrap up.
Speaker 4:That's an outstanding vision and that would be awesome. I think the question, one of the things they were trying to figure out on that question is I think the question, one of the things they were trying to figure out on that question, is is it possible that certain strains of misfolded alpha-synuclein are missing or there's a missing pathology that isn't being picked up in Lewy body dementia patients beyond the PSIN, or maybe it's a dye or something like that.
Speaker 3:Could it be something that people are missing if somebody thinks they have Lewy body dementia? So there is a lot more here that we don't know than we do know, right? So, for example, as best anyone has been able to tell, it's the same PSIN protein in all five of these diseases. So why in Parkinson's disease does that protein build up in the substantia nigra and the locus coeruleus? Why in Lewy body patients does it build up in the cortical structures and affect their memory? Why in multiple system disease does it build up in many places?
Speaker 3:And that's where people are really getting to the concept that you've introduced, which is are there different conformations of the protein? Does it fold differently and therefore dictate which parts of the nervous system it's going to go to? Are there additional proteins that fold with it that maybe shuttle it to different parts of the nervous system? Why do some people with Parkinson's eventually develop a terrible dementia, you know, and we call that Parkinson's disease dementia, because they had Parkinson's for 10 years first, and some people have dementia with Lewy bodies and then eventually develop some Parkinson's features later. It all has to do with where the protein is accumulating in the brain, and I don't think anybody has any idea as to why that is. Everyone's trying to study it and to figure that out. Your theories are just as good as anybody else's theories. Which is? Different shapes of the proteins, different other proteins, sex differences? Any of those things could be true, but we just don't know.
Speaker 1:So I know I said that was the last question but, as you're talking, I want to know how do neurologists out there know that this test is available? Because we're finding that we're telling our people in our support groups and they're going to the doctors and telling the doctors about this test, and it shouldn't be that way Because there's for the people that aren't attending our Zoom, like it's. It shouldn't be that way. So how is this getting disseminated out to the medical?
Speaker 3:professionals. We'll take some of the blame for that, which is that we launched two months before COVID hit and so our first two years really was spent just trying to email some folks and you know, patients weren't even coming into doctor's offices for a year and I mean, everybody remembers the mask, right. So we are a little behind, where we'd like to be for three years, commercialized. What I will say is I think we are now in 43 states, so neurologists in 43 states have used us. I think we have over 500 neurologists that are using us across the country. There are 13,000 neurologists. So we have only really begun to reach out.
Speaker 3:We advertise in journals, we do CME activities, we go to national conferences, but we are definitely a little behind, kind of where we'd like to be, and we do hear that patients often go in and say, hey, could you do this test? And the doctor's never heard of us. And we encourage, encourage that. So that's great, because then they call us and we get to talk to them and we can usually get them going. Um, but we we do need to try to reach out a little more broadly, um.
Speaker 1:So yeah, thank you for that. Um, we're, trust me, we're. We're kind of creating our own little I don't know what. What are we group of marchers that are just shouting at the rooftop to help one another? But anyway, due to time, we're going to have to stop there. But I really appreciate you answering, especially that final question regarding women versus men getting a diagnosis, because the person who sent that question to us had valid concerns in her struggles to get diagnosed. So thank you, wendy, for coming on and helping us with the more technical questions and, dr Levine, we can't thank you enough for what you all are doing to help get a diagnosis for this disease.
Speaker 3:I appreciate it. Thanks for having me on.
Speaker 1:Keep reaching for the stars, mister. Please keep reaching, we will try yeah.
Speaker 4:We appreciate what you're doing. Definitely, yeah, we do, actually, both of you guys, all three of you guys, thank you.
Speaker 2:Well, folks, that's all we have time for this week. Thank you again to Dr Levine and to our guest helper, wendy Kogan. Remember you can email us with suggestions on what you'd like us to discuss on future episodes, or you can ask any questions you have, and we'll sure do our best to help get you the best answer possible.
Speaker 1:And remember that Curry sometimes remembers to put to add the link to the to the weekly pod. You're doing a good job, curry. Yeah, you're slacking this week but most of the times, yeah, he does remember to post the links. Um, hey, I take blame too, because sometimes I forget to push publish and I'm like after it gets done and I'm like how come you haven't posted? But anyway, if you're interested in helping us as a volunteer and advocate, please send us an email at louiebodyrollercoaster at gmailcom, because the more people who reach out, the more people we can help.
Speaker 2:And if you'd like to learn how you can be a supporter of the podcast, please see the episode notes, as we post information on that there. Well, folks, thanks again for joining us Until next week. This is Linda and Curry signing off.