NANCY KEACH: Good morning, good afternoon. And good evening, everyone. Welcome to the 31st episode of BrightFocus Foundation’s Zoom In on Dementia & Alzheimer’s program. I am Nancy Keach. And I am so happy to see you all as always. Welcome, and thank you for attending.
As I say at the beginning of each episode, BrightFocus Foundation is a nonprofit supported by donors and people like you that has invested over $310 million in research globally to understand and treat Alzheimer’s disease, macular degeneration, and glaucoma. This entire Zoom In series that’s been going on for over two years now is supported in part by funding provided by Lilly, Biogen, and Genentech. And we are very grateful to these sponsors for making this free program possible for over two years now. So, thank you to our sponsors.
And finally, we always receive a lot of questions that are not on the topic of the particular program. So, I want to refer everyone to these 30 other episodes that we’ve done that have a tremendous amount of information. They’re free. They’re on our website at brightfocus.org/zoomin. They’re on YouTube. So if you have a lot of questions on how to get a diagnosis or on the new drugs that are now available, please go to this website. Thanks, Brooks, for putting that into the chat. And all the episodes are free, as you are aware. It’s so good to see everybody.
Today’s program is “Can GLP-1 Weight Loss Drugs Treat Alzheimer’s?” And so now I would like to introduce today’s expert guest, Dr. Paul Edison, whom I just learned, in chatting with him ahead of time, has been on the case about GLP-1 drugs long before anything about this was published. So, we’re getting this information, really, from the source. Dr. Edison is the professor of neuroscience in the Faculty of Medicine and a clinical professor in the Department of Brain Sciences at Imperial College London. He is also an honorary professor at Cardiff University, Wales. Dr. Edison’s work centers on neuroinflammation and the interplay between inflammation and immunity in neurodegenerative and neuroinflammatory diseases and relating these to genetic information. He leads the Imperial College Memory Research Center and is the chief investigator for several multicenter research studies evaluating novel treatments for Alzheimer’s and other neurodegenerative diseases. And one of these trials is evaluating the GLP-1 drug liraglutide in the treatment of Alzheimer’s disease. And that study, I believe from the internet at least, you’ll correct me if I’m wrong, is being conducted at 24 sites in the UK. Dr. Edison, welcome to the program, and thank you so much for taking your cocktail hour to join us.
PAUL EDISON: Thank you very much for the kind introduction.
NANCY KEACH: It’s wonderful, wonderful to have you. So, I’m going to start off with the basics. What are GLP-1 analog drugs? What are they, and how do they work? And explain this to us as a completely non-scientific audience.
PAUL EDISON: So GLP-1 analogs are the drugs that are used in the treatment of diabetes. So, we know that this helps with blood sugar. We also know that it has an influence on weight loss. Now, coming to Alzheimer’s disease, in the brain, these drugs have been shown to have multiple effects. It reduces the inflammation in the brain, which is seen in Alzheimer’s disease. It can also reduce tau formation. It can reduce what we call the insulin resistance, which is also seen in the brain in people with Alzheimer’s disease. And it can also reduce the amyloid formation and the toxicity due to these abnormal proteins, which we see in the brain. So, we believe this is a unique compound that has multiple effects on the brain. And that is the primary reason I thought this may be beneficial in treating Alzheimer’s disease. And we proposed this almost 15 years ago to see whether we could use this drug for the treatment of Alzheimer’s disease.
NANCY KEACH: Thank you and thank you for going back — I think most of our audience is somewhat educated about Alzheimer’s. But tau and amyloid are proteins that are found in the brains of many people with Alzheimer’s disease. And so, you are saying, Doctor, that they seem to lower those toxic proteins in addition to reducing inflammation and insulin resistance. You led a trial called ELAD, Evaluation of Liraglutide in the Treatment of Alzheimer’s disease. So, can you give us a little background, describe the trial, and tell us what you found?
PAUL EDISON: So yes, thanks. So, this study was a multi-center study, which we did in 24 sites in the United Kingdom. And so, the drug we used was one of the earlier GLP-1 analogs called liraglutide. So, it is a daily injection. So, we had patients with what we call the mini-mental test score around 20. And these patients had a detailed clinical evaluation. They had an MRI scan and an FDG PET scan. And then they went on to have a daily injection of the drug.
Along with that, they had a huge amount of clinical evaluation, including memory testing, which lasts for about 1 and 1/2 to two hours. I’ve got a lot of blood collected for looking at various parameters. These patients had about 17 visits to the different trial centers. But we did all the scanning at a single site at Imperial College London to ensure these patients have uniform data available. So, what we found was that patients who were on the treatment with liraglutide had a lower reduction of cognitive function– i.e., the cognition was better in patients who were treated with liraglutide compared to the control subjects.
Also, the volume of the brain– i.e., MRI volume– was better in patients treated with liraglutide compared to the placebo. However, I must say the primary outcome measure that we used was glucose metabolism. We did not see any significant difference between the treatment and the placebo group. However, the numbers that we studied were relatively small, so we had 204 patients to start with. And around 164 patients completed the study because there were dropouts due to side effects and various other things. So, the number of subjects in each arm of the study was relatively small compared to a proper phase III study, where we usually go for numbers anywhere upwards from 1,500. So that is the gist of the study.
NANCY KEACH: Thank you. And you said that the primary endpoint, which is what you initially said you were going to see if you could show, was a change in glucose metabolism. And you did see better cognition, less atrophy of the brain. Why was glucose metabolism the primary endpoint? What would that have shown?
PAUL EDISON: So, I was a bit surprised that the glucose metabolism didn’t come through. Having said that, the first thing that we said was, okay it may very well be because of the smaller number of subjects. However, there are a few nuances to that. One is patients who are taking the drug, which can influence glucose for a year, to ensure that the drug is not influencing the outcome measure. We stopped the drug for three days. We don’t know whether that would have had any impact on the measurement. Now I also believe the glucose metabolism is one of the different components, which makes the neuron healthy. In the sense, you have got inflammation, you’ve got astrocytic, you’ve got mitochondrial function. And where MRI is a composite measure of different processes happening. I know the MRI volume also has challenges, especially when we are looking at the amyloid agents. But yes, I think these are some of the things that we are now trying to understand. And we were very encouraged by the fact that there was some improvement in cognition.
NANCY KEACH: Absolutely. And as you reminded me in our pre-discussion, these are very early days of learning about this. And a lot more will be revealed. There was– or actually is still running the EVOKE and the EVOKE Plus trials, which unfortunately are no longer recruiting. They have filled up the study, but now they are going to be running the trial and reading out the data. Dr. Edison, can you tell us a little bit about that study? Which is global. It isn’t just in the UK, and there were many, many sites in the US. But when can we expect the results from that study, and what are the endpoints they’re looking at in that study?
PAUL EDISON: So, I think EVOKE and EVOKE Plus, between those two studies, there are about 3,600 patients being recruited to this. One of them has a small amount of vascular changes in the patients. One of them hasn’t got any vascular changes. But all the patients should have amyloid in their brains to enter the study. And these patients have cognitive measures as the primary outcome measure. And the study is being conducted, as you mentioned, in 600 sites in over 40 countries. And it is sponsored by Novo Nordisk. We hope to hear the preliminary results at the CTAD this year. And that is an interim analysis of the data after two years. And after three years, the data will be out next year. Around this time, they should finish recruiting. Sorry, following up on those patients. The recruitment is already finished.
NANCY KEACH: So, CTAD is the Clinical Trials on Alzheimer’s Disease annual conference. And that will be in November. So perhaps after November, you can come back and help us understand this preliminary data.
PAUL EDISON: Yeah, I would be delighted.
NANCY KEACH: That would be great. And then you’re saying that really the conclusion would be, when, another year after that?
PAUL EDISON: That’s correct, yeah. So, it will be another year to finish the study.
NANCY KEACH: And before I start to jump into some of the questions that were asked, are there any trials that you know of that are currently recruiting in the US for GLP-1s? Because I could not find them. But I know our participants who come to these Zooms, many of them are looking for trials to participate in. So, I just wonder if you know of any.
PAUL EDISON: Yeah, at this moment, I’m not fully aware of many studies that are happening. I think most people are waiting to see what happens with this phase III study. That’s why there’s a bit of a waiting game to see if things are positive. And I’m sure there will be plenty of studies that will spring up.
NANCY KEACH: Yeah. There were many. Anne from Green Valley, Arizona, and Steph from Martinsville, Virginia. A lot of people are asking, are there current trials? So, I’ll just tell the audience that if we, if BrightFocus, if we do learn anything or launch, we will let everybody know about that.
So, Lisa from Lancaster, Massachusetts, asked, and many others about safety. Are these drugs safe in general, and are they safe for the long term? And do you think, this may be too early to know this, that if they are effective in Alzheimer’s disease, you’d have to take them for your whole life? And we’ll get into stages later. But basically, let’s start with, are they safe in general, and are they safe for the long term?
PAUL EDISON: Yeah, so if we were to look at the side effects of these drugs, the main side effects are nausea. Some people do get diarrhea. And the other important side-effect is weight loss. Previously, there was some concern about whether the patients could get pancreatitis. But I think from the clinical population in diabetes and other obesity, the number of patients who get that is very, very minimal. Like any drug, these GLP-1 analogs also have more side effects.
So, in this study, which we have done, which is the ELAD study, these are patients who are non-diabetic. So, these patients are patients with Alzheimer’s disease, which we see in the clinic. But we excluded patients with diabetes. And what we found is that the majority of the patients did tolerate the drug very well. A proportion of patients did have nausea and vomiting. A couple of patients out of the 200, we had to withdraw the drug immediately within two weeks because they had severe nausea and vomiting. So, they couldn’t continue with the drug.
Around 20% of the patients had weight loss of less than 5%. Now, it was statistically significant compared to the control. So, there is some amount of weight loss. And bearing in mind that these drugs can cause weight loss, the treatment for obesity, but that was not particularly significant in the sense that we didn’t make a clinical decision that the patient should be withdrawn from the treatment because of the weight loss. Well, if the weight loss is significant, sometimes we make the decision that the patient should be withdrawn. But these could be monitored, and the dose could be titrated, et cetera, et cetera.
NANCY KEACH: And Cheryl asks in the chat, are the patients in that study taking a full dose of the medication or a microdose? We did have several questions about microdosing. So, I think from Stephanie in Escondido, California, Rochelle and Melissa in Dubuque, Iowa. Yeah, is microdosing beneficial? So, can you explain that?
PAUL EDISON: So yeah. I mean, at this moment, we don’t have any evidence for microdosing. So, the patients who are in our study, what we used was the dose that we used for diabetes. And our aim was to make sure the patients are on the maximum dose for diabetes. Not the maximum dose for obesity, which is much higher. So, the maximum dose, which we use for diabetes.
We did that for two reasons. We wanted to make sure these patients get the maximum treatment when we are testing it, at least. Now there are a lot of questions about whether we need that full dose or whether we can get that effect with microdosing. The short answer is that, at this moment, there is no evidence to suggest microdosing will be beneficial, because no studies have been performed to test that. So yeah, I mean, I think the short answer to that question is we need to perform another study of the scale, which is what is happening with the two large studies. Then only will we have a better idea.
NANCY KEACH: Yeah, and from some of the questions in the chat, it sounds like there’s confusion as to what a microdose is. Because, as you mentioned, the dose for someone who’s diabetic is much less than the dose used for obesity. And so, Rochelle is asking, what was the maximum dose that you used?
PAUL EDISON: So, for the liraglutide, the maximum dose was 1.8 milligrams per day, which is what is allowed for diabetes. So, the equivalent dose for the oral semaglutide is 14 milligrams per day. But with the subcutaneous injection, the doses are much lower. It comes as one milligram, which is the maximum dose that they use.
But now the question about microdosing is very interesting. What is the right dose? And to have that answer, we need to do clinical trials with different doses and a large number of patients. Then only will we have a definite answer to whether it is beneficial or not.
NANCY KEACH: I’m going to continue with some of the previous questions about safety. As I think a lot of our viewers know, there’s a genetic predisposition, if you are APOE4 positive– I’m seeing heads nodding– that you sometimes are not included in trials. So, are the trials including patients with APOE4? This is from Chris in Honolulu. And is it safe for people who are APOE4 positive?
PAUL EDISON: Yeah, we do not believe that there is a particularly increased risk in patients with APOE4 positive, because the mechanism by which it acts is slightly different from the anti-amyloid agents. So, I think so far, the evidence is that there is no particular difference between the APOE4 patients versus known APOE4 subjects. At least, that is my best understanding.
So, I would imagine that would be the case, even if the wider study, the bigger study, we were to report. At least mechanistically, we do not think there should be a significant difference.
NANCY KEACH: I know clinical trials have to be very restrictive in their inclusion criteria. Don’t be on any other drugs and don’t have other conditions, so that you can really see in a clinical trial if a therapy is working. So, I don’t know if you can really answer this. But we had a lot of questions. Marion from West Palm Beach, is it safe if you’re taking antidepressants? Pat from Henderson, Nevada, and Toby from South Orange, New Jersey. Many others. Is it safe to take these drugs if you’re on Leqembi or Kisunla infusions? If you’re taking Aricept or Namenda. Can you comment on these at this point?
PAUL EDISON: Recently, I gave a plenary lecture at the American Academy of Neurology. Some of the things that I said were my speculation. But what I could say is that there is no real reason to believe that this will have adverse effects with antidepressants or anti-amyloid agents. There is some debatable data about antidepressants, but there’s some suggestion that some people may feel a bit low with these compounds. I don’t think the data is strong at this moment. But to say whether there is any major side-effect, we can’t see the evidence that supports it at this moment. So, I would say like patients with diabetes, but none of these patients are excluded from having these injections or oral tablets. The patients who are having other medications can also have these GLP-1 analogs, whether it is licensed for Alzheimer’s disease or any other drugs.
NANCY KEACH: And Mary just put in the chat, and somebody, Will from Pensacola, Florida, is asking, what about GLP-1 drugs causing eye problems? And Mary said she read some news articles recently about GLP-1s and blindness. Is that an issue?
PAUL EDISON: Yes, that is a very interesting point. And it’s an important thing. So, there is one condition, called macular degeneration. I think there was one report mentioning that it got worse with the GLP-1 analogs. So, I think we need to learn more about that. What exactly is happening there? Normally, we would have thought it could be beneficial. Because what it promotes is the integrity of the vasculature. And hence, we thought it would reduce the stroke and so on. But it was surprising to see what happens in macular degeneration. So yeah, I think we need more data to find out what exactly is happening there, what evidence is there, and probably prospectively looking at a large number of patients, and whether this is happening or not.
NANCY KEACH: I want to just say, you’re very brave to answer all these questions at such an early stage of understanding these drugs. So, I just want to say how much I appreciate that, because I know it’s not easy when we’re just really at the cusp of understanding how these work. So, Melissa, in your study, was there any reduction in bad cholesterol?
PAUL EDISON: Yeah, so we didn’t actually look at the cholesterol, because most of the patients we did– I mean, being Alzheimer’s disease, I was surprised to see there were not many patients who were overweight or had high cholesterol. Partly because they were slightly on the leaner side, and again, with the small numbers, I wouldn’t be able to make a definite assessment on that, because I don’t want to give the wrong impression.
NANCY KEACH: I’m looking for it in my notes. Yeah, here. Lisa from Tempe, Arizona. She said, what about Alzheimer’s patients who are already thin or even too thin? Is this a safe alternative for them? And so, I have to say, there were actually a lot of questions saying, there are even some people who are trying to put on weight or eat proteins. Or so would it be safe, potentially, for them to participate in a trial or use this drug for Alzheimer’s?
PAUL EDISON: So, the first thing I would say, as we were discussing, is that we still need to learn a lot more about these drugs. Now, again, from the safety point of view, what we know is that people have a tendency to lose weight. We can monitor that. And we may have to make a clinical decision, OK, this is not the right for that particular patient, or not. If the patients are already losing weight, I would say it is probably not the best drug. But in those circumstances, we should also find out what exactly is the reason to lose weight.
So, there are two things to that. If people are complaining of weight loss, and especially if they are slightly older, there are other things that may cause weight loss. So that needs to be considered before attributing everything to the drug. Equally, the drug can cause weight loss, but I would say never attribute everything to the drug unless we have excluded other things. That’s one of the things that I have also learned from doing the study.
NANCY KEACH: I have a great YouTube question from John; can’t you do real-world evidence to monitor those on a weight regimen to see if they have a better brain?
PAUL EDISON: Yes. So, I think that’s a very good question, John. There are several studies happening to see what happens in the real world. Whether there is any beneficial effect, et cetera, et cetera. Real-world studies add evidence to the evolving evidence that we’re already having from retrospective studies. But the challenge is that regulators won’t accept that as the definitive trial to approve a drug. For that, we need a prospective study with predefined outcome measures. Then, only a drug will be approved formally by most of the regulators in the world. So, as much as we are able to collect the data and gain information about the drug, we may not be able to get the drug approved by the authorities. So that’s the real challenge. And it’s a shame.
NANCY KEACH: It is a shame, and it is a real challenge. And Wendell asked, was this clinical trial published, and where? And I think Brooks put the link in the chat previously. But Brooks, if you could put the link in the chat again, that would be terrific. Yeah. Robin and Steve, do you have to take this drug forever? What happens when you stop? So, I know, again, we don’t really know. But what would you project?
PAUL EDISON: Yeah, so my conclusion for, I would say, for my plenary at the American Academy was that this may very well be like a statin. So, it’s more than likely to be a statin. So, it may help with preventing dementia, but it will also be useful in people who already have dementia. Now the question about whether we may– I mean, most of the drugs were being licensed for Alzheimer’s disease or other diseases, for that matter, even in the non-neurological conditions.
Unfortunately, we have to take the drug for a long time, whether it is for blood pressure, diabetes, to prevent stroke, or aspirin, or things like that. So, I would be surprised if it turns out to be anything other than the other drugs. That means you may have to take it for a long time.
NANCY KEACH: Again, we’re projecting here. But there were a lot of questions about at what stages of Alzheimer’s this could be used. So, I’ll ask you to go out on a limb here, and we won’t hold you to it. But several people asked, could you start taking it– they have Alzheimer’s in their family– and could you start taking it for prevention? Is it only effective in the early or middle? Can you take it if you’re in an advanced stage of Alzheimer’s? Do you have any sense yet? Or maybe we will know a little bit more from EVOKE and EVOKE Plus, how will this be useful at what stages of Alzheimer’s?
PAUL EDISON: Yeah, so I think that the studies that are happening are in patients who are amyloid positive. So that means they have got some evidence of Alzheimer’s changes happening already. In these two studies, there are patients who are reasonably early in the disease trajectory as well as those with pretty full-blown Alzheimer’s disease. Now, my projection, it is purely my speculation, is that with the right compound, we may be able to prevent Alzheimer’s disease.
What I’m trying to say is that if we were to use this in the very early stages, it may at least delay the progression of the disease. And hence, I use the analogy of it may very well be like statins in cardiovascular disease for preventing heart disease as well as stroke. That’s my prediction and may very well be wrong. But I think we hope with the right drug, because of the unique properties of this compound, there is great potential. And I’m also encouraged by the fact that every month, if not more frequently than that, independent studies are coming, demonstrating the same effect. So, I’m encouraged by the results that are happening.
NANCY KEACH: I’m going to go out on a limb with you, although I’m not a scientist, and say that I think this is incredibly exciting. And at the same time, I’m thinking about the combination of drugs. And we’re having another upcoming episode on gamma wave treatments, which seem to have positive data. And last week, we had Dr. Robbie Brinton on talking about the potential for regenerating brain tissue. And so, as I’m thinking about this, do you see a time where you think this drug, used in combination with other drugs or non-drug treatments, can really prevent the onset of Alzheimer’s dementia?
PAUL EDISON: Yes, definitely. I mean, if it were to be positive. And I think that is the future. So, part of the reason why I believe that this drug could have an effect is simply because of the multiple actions that these drugs have on different proteins, which are building up in the brain. However, we know that the more the agents can have– so if you were to say what would be the ideal treatment for Alzheimer’s disease, this would be multiple drugs. We know that different proteins are there, and there is– even though we believe one protein has an influence on others, there’s no reason to believe all these proteins are dependent on one protein, i.e., amyloid.
So, the processes happening in the brain can be independent of others. Hence, we may need multiple drugs. And GLP-1 analogs are going to be one of the multiple drugs to prevent and treat Alzheimer’s disease. And so, there is no doubt that it could be used in combination. I mean, even what we have tested is on the people who are already on cholinesterase inhibitors and memantine. So, it’s on top of that. So clearly, those would be the way forward even if an anti-amyloid or any other new drug comes to the market.
NANCY KEACH: I have several questions, but I’m going to jump to– and again, do you project, because we don’t know this, a lot of questions about whether these drugs might work for other types of conditions. This is Peter from Portland, Oregon. Is there any GLP-1 experimentation around primary progressive aphasia? And Jody from Short Hills, New Jersey, for autism. Ron from Denton, Texas, for Parkinson’s. There were also questions about Lewy bodies, frontotemporal dementia, and the Down syndrome population. So, we’ll put you back out on that limb. Do you think there are applications for these other conditions?
PAUL EDISON: I think the property of the GLP-1 analog is a class effect as a mechanism by which it improves brain health, to put it mildly. So, there is no reason why it cannot have an effect on neurodegenerative diseases, particularly frontotemporal dementia and Lewy body dementia, and so on. I myself am trying to do a study on frontotemporal dementia. And there are some applications to look at other forms of dementia, too. There are studies which is already happening in the field of Parkinson’s disease. There are some studies that have shown a positive effect, particularly with lixisenatide. However, biduran, which is the exenatide, the long-acting, did show a negative effect. However, I may have to highlight that the number of patients studied in these studies is relatively small. So, the number of subjects is relatively small, which makes it much more difficult to interpret. So, a large number of studies are necessary to make a real assumption of what exactly happens.
NANCY KEACH: Portia asks, how far are we timewise from possibly using this for treatment?
PAUL EDISON: I think if next year, if the EVOKE/EVOKE Plus, which are the GLP-1 analogs in Alzheimer’s disease, which is a phase III study conducted by Novo Nordisk, if those results are positive, the primary endpoint meets the trial outcome is the primary endpoint. Then it is only a matter of regulators approving it. So, I think that the critical time period will be next year to see where we are with the drug. Compared to other drugs like anti-amyloid drugs and stuff, these drugs are now available as oral medications, which gives them much easier accessibility to the patients. And the storage and things are relatively easy. So, I would say if the trials are positive, it will be available very soon. Clearly, there is a big if.
NANCY KEACH: And hopefully, yeah, hopefully we will have some indication within the next year.
PAUL EDISON: That’s correct.
NANCY KEACH: So, I’m going to ask, if I were concerned for myself and I do have Alzheimer’s in my family, I’d probably want to go get on one of these drugs now. And I’m sure there are a lot of people here who are saying, well, why do I just get on it in case? Now, there are a lot of different GLP-1s or several different ones. Do we have any indication yet as to whether there may be more effective than others in terms of brain health, let’s say?
PAUL EDISON: At this moment, we haven’t got any evidence because there haven’t been many ever tested. But we believe the GLP-1 analogs, which could enter the brain, may have a better effect than some of the things that don’t enter the brain. And so that’s the first thing. So, one of the things that I would say is we need to better understand how much these drugs get into the brain. Interestingly, some of these drugs, particularly the GLP-1 analogs, are currently being tested. But there’s a big debate about how much it gets into the brain. So, there is room for quite a lot of improvement in the drugs themselves.
NANCY KEACH: Yeah, that’s interesting. Because how does it work? Do we know how these drugs do this? It’s a YouTube question from John. Why do they work? What do they do? You described that a little bit. When you’re talking about getting into the brain, I’m wondering if you’re saying that there might be a case, for example, where you’re using focused ultrasound to open the blood-brain barrier so that you’re getting more drug into the brain? I know that’s a long leap. But is that the type of thing you’d be potentially studying?
PAUL EDISON: Yeah, so at the moment, there are several GLP-1 analogs. Some of them, we know, get into the brain better than others. Now, more than focused ultrasound and stuff, which is a bit more complicated at this moment to have in daily practice, or say, for instance, a large number of patients. It will be easier to actually modify the compound in such a way that it gets into the brain. Much, much better.
So, there are also people developing small molecules that can get into the brain. So, there’s quite a lot of activity happening because of the potential of these drugs in treating Alzheimer’s disease and other neurodegenerative diseases. So, there’s a lot of work happening trying to see whether we can get these drugs into the brain better. But yeah, that’s quite, quite a lot of research happening. At this moment, what we know is that if any drug gets into the brain, it should do better than those that don’t get into the brain.
Now, the question about how they work if they don’t get into the brain is that we think that the effects– there are two things on that. One is if you’re taking a drug for a year, even though most of the measurements we do are direct measurements of the drug in the brain. But it is likely that these drugs can have an indirect effect on the brain. And the second thing is that even our measurements of how much gets into the brain are satisfactory to interpret the results of a person who is taking the drug on a daily basis for months and months and months. Then, whether the systemic effect– i.e., what happens below the neck and in the other organs– has an effect on the brain. And I believe that also plays a significant role in the mechanism by which these drugs are acting.
NANCY KEACH: Yeah, that’s so interesting. And I’ll mention that I think, and Amanda will know, we have Dr. Beau Ances coming in within the next month or two to talk about the gut microbiome and the brain. So that’s interesting when you’re talking about below the neck, there obviously still are connections. And Jim wrote, dulaglutide has the highest brain levels. Are you familiar with this?
PAUL EDISON: Yeah, he’s absolutely right. Interestingly enough, dulaglutide crosses the blood-brain barrier better than the other compounds. But I don’t think there are many human studies done on dulaglutide. So yes, it’s absolutely correct.
NANCY KEACH: Thank you. And two questions about tirzepatide. I don’t know if I’m pronouncing it correctly. Did you test tirzepatide, too, and is it similar to semaglutide? And a YouTube question from Susan: Does GLP-2 tirzepatide work better?
PAUL EDISON: So, yeah. So tirzepatide or Mounjaro, it’s– so we haven’t tested– we are still in touch with various people to test that. However, we know that tirzepatide has better weight loss properties. But whether that will translate, it’s difficult to say. So, the short answer to your question is, we don’t know yet at this moment. And I don’t want to speculate on that, because these are two different companies, compounds, et cetera, et cetera. So yeah, I think there would be more activity happening immediately after the results of these upcoming studies are out.
NANCY KEACH: And I’m going to commend the– I don’t know how many people are still on YouTube. But the 120 people that are still on Zoom, thank you for hanging in here with us when this is, as we can see, still in the very early days of understanding. But it’s really fascinating and also really represents how we learn how drugs are developed and how we learn how to treat diseases. It’s very heroic, I think, the scientists who work on these conditions and then get scrutinized a lot. So, thank you for staying with me, because I think it helps understand the process of how we have to prove and how we learn what we know through science at a time when, in the United States, science is rather under attack.
So, I think your dedication here shows that you want to understand this process, and we’re very grateful for that. Tanya wrote; do we have any idea of whether these medications will ultimately be able to reverse Alzheimer’s symptoms?
PAUL EDISON: Yeah, that’s a very important question. But that is a very difficult task. So, I think that the best we can hope for, for most of the neurodegenerative diseases, is prevention, rather than reversing the symptoms. So, I think if we can prevent it, that would be a success. That’s what I would say. To reverse the damage which has already happened, it’s much more difficult to achieve, at least in the next decade or so, let’s put it that way.
NANCY KEACH: Yeah. I get questions all the time. We have thousands and thousands of questions that have been submitted. Is there anything to do for someone who is already in the late moderate or advanced stage? Well, we don’t know yet if this would ever have the possibility of reversing the damage that’s been done. I’m just wondering if this is something that can get tested in moderate or late moderate Alzheimer’s.
PAUL EDISON: Well, there is no reason why it shouldn’t be tested, that is for sure. Clearly, some of the things that we need to consider are weight loss and other related side effects on these patients. The route of administration, and particularly having an oral medication, makes it slightly easier, because then we can say OK, particularly from the period where we are testing these compounds. Giving daily injections to a person who cannot give consent is a much more difficult task. But if it’s an oral medication, it makes it slightly easier from that perspective.
NANCY KEACH: Ah, OK. That’s really interesting. Mary asks, does it matter if the semaglutide is compounded?
PAUL EDISON: Well, I don’t want to comment too much. As you know, it’s a very debated question. And also, the regulators and no one noticed themselves are fighting against the whole concept and stuff. So, I would probably keep well away from answering that. I’m sorry.
NANCY KEACH: Not a problem at all. Yeah, everyone who’s asking, I’ll just say it out loud for those who aren’t reading the chat: yes, there will be a recording of this presentation emailed to everyone who is on. It will also be put for free on our website, which I will reannounce at the end of this presentation. And gosh, thank you all for your incredibly kind comments. This is a surprise, and I really appreciate it. There are a lot of comments, Dr. Edison, thanking us for the presentation.
I want to ask something that’s a little more general here. But I think it takes so many years and so much money to do these long-term studies, clinical trials, and research studies. And this is a terrible question to throw at you, but I’m doing it partly because you’re not in the US. Do you see ways that we could increase the speed and lower the cost of some of these clinical research studies so that we can get approval for therapies more quickly and get new novel therapies for dementias to patients more quickly? Because this is such a massively common condition, and it so desperately needs therapeutics. So sorry to throw something so broad at you, but you’ve been at this for quite a while. So, I’m wondering, is there any low-hanging fruit that you feel comfortable stating could make these trials quicker and less expensive for the public?
PAUL EDISON: No, it’s a very important question. And even as an academic, as you can imagine, I’ve been frustrated trying to set up the things, get the funding, get enrolling the patients, and the cost and coming up with them. This requires some international collaboration and significant collaboration with the industries. So, where there will be mileage is where we can say, OK, we got one study, you got the patients. Already, they have at least the control data. All the data are collected in a uniform fashion. So, we need to just add patients to that.
So, the platform idea, where we are testing multiple drugs, is a good one. Then that also becomes whether– I mean, this is purely my own view. Depending on the side effects of the compound, whether the regulatory metrics could be slightly changed. Because it’s one thing to have a drug that has a significant side-effect versus a drug that has minimal side-effects, and we build the evidence as we go along. So that’s one approach that could be taken. But I don’t think the regulators are going to easily change it. But I believe there is a strong– say, for instance, if you know drugs, aspirin, or statins, if they are safe in other diseases. And if you want to test in a new condition, you don’t have to have the same regulatory standard as the compounds, which are likely to kill people, for that matter. So that’s one approach that could be taken, rather than saying that all the drugs should have exactly the same method of approval. And I’m sure this is the most controversial, but I’ll put it out there.
NANCY KEACH: That’s wonderful. I will thank Dr. Edison, whom we have not met before, but I have to tell you how much I appreciate your putting yourself out there, as you said, for this presentation and sharing your knowledge, really having been a pioneer in this area. So, thank you so much for participating today, and we will ask you to come back when we have some further results.
PAUL EDISON: Thank you very much for inviting. It’s great to talk to you and thank you very much for the audience.
NANCY KEACH: Absolutely. So, for our audience, we have free resources available. You can go to brightfocus.org/zoomin. If you want to request copies of any of these brochures, you can see the number to call on the screen. 855-345-6237. Or you can email reply@brightfocus.org.
If you believe this program would be helpful to someone you know, please help us get it out there by sharing this link with at least three friends. More, if you can. brightfocus.org/zoomin. This program has been growing tremendously. So please continue to share it so that it’s of use to as many people as possible. And is there one more slide, I believe? Yes.
So, on September 18, we have “Gamma Brain Waves & Alzheimer’s: Update on the HOPE Study,” which is really fascinating. And also, I think we’ll be reading out our data either at the end of this year or next year. And you can watch previous episodes, as we mentioned.
There’s one more comment from Terry. Dementia patients and relatives are desperate for a cure and, therefore, are at risk of being taken for an expensive ride. That is true. I say to sign a consent now to give informed consent that they can experiment— I think what Terry is saying is to your point about not being able to give consent, say, for an infusion, if you are past a certain point in your dementias, that if you are caring for a loved one who is not advanced and can do some kind of a– get their wishes known ahead of time. I mean, this is a very big discussion in caregiving and really is a legal question. And we are actually considering doing a different series on some of the legal questions and also the financial preparation questions. How to prepare for these types of things financially, for yourselves, and for your adult kids and your younger kids. So just now, we are looking at all of those angles.
And so, since we are out of time, I am going to just, again, thank you all so much for participating. And as I always say at the end of this, hug everyone you love. Hug them all the time. My 95-year-old mom, who is in the middle stages, was just here with me last week. And I actually had ChatGPT write her a sonnet. And we were telling her about ChatGPT. And I said, write a sonnet to Judy, who’s the most wonderful mother in the world. And it turned out. Well, she flew home to West Virginia from the West Coast, and she called me the night before last, and she said, Nancy, I found the most beautiful poem that you left me. It’s so beautiful. It’s almost Shakespearean. She said, and I’m just overwhelmed with how beautiful it is. And even though that consequence was unintended, I have to say I was so glad that she felt– she said she thought I had left it in her suitcase for her.
So, life is short. Tell everyone you love how much you love and care about them. And thank you for participating, learning, and trying to learn as much as we possibly can about these diseases. And again, Dr. Edison, thank you so much. I hope you have a wonderful evening. And we’ll see you back again soon. And we’ll see everybody in September. Enjoy the last days of summer. And thanks again.
PAUL EDISON: Thanks very much for inviting. Thank you very much, everybody. Bye-bye.
NANCY KEACH: Bye-bye.
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