Episode 76: Alzheimer's medication update

 Dr. Edgardo Rivera from Charter Research discusses the latest Alzheimer's drug on the market and the company's role in its development. The podcast delves into the complexities of Alzheimer's disease, including the roles of amyloid and tau proteins in brain degeneration. 

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Transcript

Robin: . Welcome to Informed Aging, a podcast about health. help, and hard decisions for older adults. I'm Robin Rountree I'm a former family caregiver.
I've worked in the home care industry, and now work for the Alzheimer's and Dementia Resource Center. With me is my co host. 
Edith: Thank you for joining us today. I'm Edith Gendron, Executive Director of the Alzheimer's and Dementia Resource Center. I have 40 years of working with adults, primarily with seniors and elders in need.
I'm a certified Positive Approach to Care trainer and consultant, and ADRC is a designated Positive Approach to Care agency. 
Robin: Now the thoughts and opinions expressed here belong to Edith and I, not our wonderful employers and sponsors. This podcast is a service of the Alzheimer's and Dementia Resource Center.
We are not affiliated with the Alzheimer's Association. Before making any significant changes in your life or your person's life, please consult your own experts. [00:01:00] Today, we're talking to Dr. Rivera from Charter Research about the latest Alzheimer's drug that is on the market and what Charter had to do with that.
So stay tuned. 
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For more information, log on to SeniorHelpers. com slash Orlando.
[00:02:00] 
Robin: we are back with Dr. Edgardo Rivera with Charter Research and, , an impressive bio if I do say so myself, uh, I know what the MD stands for after your name, but not the FACEP. What does that mean? 
Dr. Rivera: Yes. Good afternoon. Thank you for having me here. F A C E P means Fellow of American College of Emergency Physicians.
Robin: Oh, so you're the guy who's good in a crisis, I hope. Yes. 
Edith: We needed you this morning. 
Robin: Yes, we did. 
Dr. Rivera: I heard, yeah. 
Robin: So you've been the principal investigator or sub investigator on more than 40 clinical trials [00:03:00] across all phases of research, including Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease, , particularly experienced as principal.
investigator in clinical Alzheimer's disease. Um, you also have been an invited lecturer and speaker at multiple local, regional, national, and international education and scientific meetings. Plus he served on the editorial board of two prominent peer reviewed national scientific journals for 15 years.
Edith: Holy cow. 
Robin: I know. A little intimidating. It's 
Dr. Rivera: a lot of words. It's 
Edith: a lot of work. 
Robin: It is a lot of work. So you've come to Charter. And, , there's this new drug for Alzheimer's. So first let's kind of go into what is Alzheimer's in the brain? What are we trying to fix up there?
Dr. Rivera: Very interesting question. So Alzheimer's in general, uh, we know that it's a multifactorial, multi, , causative, , type of disease is in general a [00:04:00] degenerative disease. 
Robin: Degenerative. 
Dr. Rivera: Okay. That, that means that it is going to. Continue getting, , more decline, more decline until the brain kind of like, uh, degenerates and, and parts of the brain stop working.
And some of the cells start kind of like dying as well. Mm hmm. , individually. So , because of that, it's always declining. it's not going to stop. It's going to, always going to decline. Some people at a faster rate than others. But they are going to. continue declining. The possible causes are a number of them.
However, the main hypothesis that we've been working on for many years now is the amyloid and tau hypothesis. Okay. They can come together or there is a subgroup of people that think that the Tau, the tau pathology is different than the amyloid pathology. But the conventional wisdom is that one comes after the other.
Robin: [00:05:00] So is this something that the brain creates, creates amyloid and then some people get rid of it and some people don't? 
Dr. Rivera: To some extent. So we all have amyloid. So that's, that's something that the brain and other parts of the body will create. That's a protein that is important for a number of metabolic, , functions in the, tissues.
So what happens is that in Alzheimer's in particular, the amyloid that is supposed to be nice and flowy and doing its job around, then for X or Y reasons, and there's a number of them, it gets defective. So it starts folding in the wrong way. And because of that, it gets hard and starts forming little clumps.
Those clumps at the beginning are floating and still going around with the flow of the rest of the normal amyloid. , but eventually they start, , clumping together, a small clump with another, and . Um, you know, making that size bigger until they are to be that [00:06:00] they can't float anymore and , they adhere to the, to the tissues and form a big plaque.
Robin: Okay. 
Dr. Rivera: And that's, the one that many of these, uh, drugs are, are attacking. I should say, however, that there is a number of researchers that, uh, I think that the, the clumps that are still floating are more toxic than the actual plaque because the plaque is stationary in one area, that other form is going around and doing, doing more damage, damage in different places.
Yes. 
Robin: So I guess I think of plaque the only way that I know of. that I relate to is like in your teeth. So the, the plaque, it's just that buildup that becomes harder. That makes sense to me. And then the tau, that's T A U. 
Dr. Rivera: Correct. 
Robin: What's going on with that in our brains? 
Dr. Rivera: So the plaque in the teeth is a, is a great analogy, and I use that a lot , , to explain some patients, because that's what we know.
So the tau is another protein that also [00:07:00] is supposed to be fluid, but that That one is inside the cell. The amyloid is outside the cells, in between the tissues. The tau is inside. And it's an integral part of, , tubules, microtubules, that are inside the cell , that have, neurotransmitters and other things that bring information from one side of the cell to the end of the cell, where that, , Cell is trying to communicate with the next cell.
So, , that's how, when it starts getting, , hard, then the same principle than the amyloid, but now being in those tubules, then, , start getting, what we call Tangles, and those are kind of like a bunch of spaghettis, , being tangled within the area. And that tubule, , is not integral anymore.
It's, it's not full and nice and strong. It starts not working correctly. 
Edith: Let me segway off a minute. Robin's used to this. I take us over here in the weeds a [00:08:00] little bit as you're talking when you talked initially about the floating clumps, if you will, or the floating bits of amyloid.
The glymphatic system has been described to me anyways as producing glial cells that clean up the detritus of the brain, which is why we should sleep for seven hours. If that doesn't happen, then it compromises our brains and I don't want to say accelerates, but certainly contributes to the development of Alzheimer's disease.
Do you agree with that? 
Dr. Rivera: Yeah. Yes. Uh, so that's an excellent question. So in, in that, , In that formation of the, or that function of the amyloid, there's always constantly some form of the amyloid that is going to be defective. However, , the balance remains, in a good way because of the glial cells and other macrophages that are [00:09:00] clearing those defective ones.
If you will, they are the quality control group that goes around and when they see a bad molecule that is too hard, they take it out. What happens is that as they get bigger and bigger, that is way too big of a bite for them to take. So now the glial cells and the macrophages are not effective anymore on clearing that amyloid that is being defective.
So that balance of good amyloid, bad amyloid that is constantly , being produced and, being defective. And these cells are constantly looking for them , and clearing them out. Now they are too big and they can't clear them out and starts clumping more than they can deal with. So that balance is now, , It's not on balance.
Yeah. 
Robin: So can I try to put that in layman's terms or Robin terms, which may be even simpler. So our body has a natural [00:10:00] way of cleaning up the gunk that happens in our brain. Think 
Edith: Pac Man. Remember the Pac Man little guys? 
Robin: So the little garbage truck comes along while we're sleeping, right? And tries to clean up everything.
Dr. Rivera: Well, it really happens, constantly all the time, all the time. Of course, when we're sleeping, other functions are also, uh, and then they're recharging the battery. So is, is like the snow truck, 
Robin: right? Not here in Florida, of course, but in the garbage truck, yeah, 
Dr. Rivera: that, that's right. That now they are working with no other interruptions, and they're a little bit more effective than when they had to work at, you know, uh, rush hour at 5 p.
m. with a bunch of other vehicles. Now they can't work very effectively, but they're still doing it. 
Robin: Okay. 
Dr. Rivera: Uh, uh, during sleep, they're a little bit more effective on what they do. Yes. 
Robin: I mean, our bodies are just fascinating. But they didn't come with an instruction manual. 
Edith: A neuron alone. Right. That's fascinating.
Robin: Right. Right. [00:11:00] So you've got to, as a researcher and scientist as well, have got to look at this situation and go, okay, is it the garbage truck that's not working? Is it the plaque that's building up? Or is it the little thing that's whipping through that that's the problem? And that takes a lot of time to figure out, doesn't 
Dr. Rivera: it?
It does. Because that's why these drugs take so long to be approved. And we. We take so long to go through a study because we're trying to figure that out. Exactly. , is it a production problem that is too much production? Is it a clearance problem that is not clearing fast enough? Is it a combination of both?
Is it that. This is, creating problems, but in turn is also triggering other problems, which is the tau theory as well. That part of the amyloid increasing and the plaque formation creates inflammatory processes that eventually trigger the tau to also go defective. So yes, you're right. We have to figure all [00:12:00] those things out.
And in between of that, we have to. , care for the patient. So these are participants that are voluntary, voluntarily participating in this, in the study. So we have to be sensitive to, to that as well. So it takes time. Yes. 
Robin: Wow. So you said inflammation and I know that's a bad thing when it comes to our hearts and our lungs and 
Edith: everything, 
Robin: everything bad thing 
Edith: for everything.
Robin: But is that going on in the brain in Alzheimer's? Yes, ma'am. 
Dr. Rivera: Okay. That's one of the , main theories about all these , different, , causalities of Alzheimer's is inflammatory processes. 
Robin: So this is why it's so difficult to say eating green beans helps or doesn't help because first we have to figure out what's going on and then we have to figure out why that's breaking down and that's going to be another 10 years.
But we can kind of see the people. who have gotten Alzheimer's and who haven't and compare like healthy habits. Like right now we believe that maybe a more [00:13:00] plant based lifestyle is better for the brain. Correct? 
Dr. Rivera: Yes. So, but, but there's no magic bullet. So this is a multifactorial type disease and therefore is a multi pronged approach to Try to stop it or reverse it.
So one of them is exactly what you just said is, is your healthy, , nutrition. So I'm not going to use the word diet because people immediately go to a different place by thinking diet. Oh my gosh, I'm going to do the Atkins diet or this diet. No, it's not diet. It's nutrition. So, , healthy nutrition is what we need to do.
And that's what we don't do ever since we're kids. So at the last stretch, when we are 65, 70, 75, that we're having a little trouble, then we go, Oh my gosh, I need to, uh, get healthy nutrition. And then we try to kind of like scramble and, , undo what we have done for 65 years. Yeah, 
Robin: and your body doesn't really [00:14:00] appreciate you cramming for the test, does it?
Edith: So all the mothers, and all the grandmothers, and fathers, and uncles, and aunties, don't feed those babies sugar. 
Robin: Yes. Special occasions. No. No. No. No. 
Edith: Why would we want to give our kid poison on a special occasion? Oh my goodness. I know I'm tough on sugar. You are. 
Robin: Okay. Let me. If that wasn't enough, I'm going to throw some more on the fire.
Dr. Rivera: So , it's all about moderation. And it's all about what is right. We need sugar. That's the main substrate that we, that we utilize. How, how we're going to get that sugar is the important part. If we're going to get it highly refined and if we're going to get it all the time left and right. And if it's going to be a reward for the kid , then you're using the, the correct term, you're rewarding them with poison.
Uh, so all that type of relationship with food [00:15:00] is what needs to be readdressed and reinvented. Uh, it's not like, no, I'm not going to eat sugar at all. Yeah, we do need sugar, but how am I going to do that? 
Edith: I should have clarified. Added sugar. Yes. Yes. Naturally occurring sugar. The apple is good. The orange is good.
The banana's good. 
Robin: The 
Edith: grapes are yummy. The dates are wonderful. Especially those little golden dates that turn brown, they taste like butterscotch. Love them. Anyway. 
Dr. Rivera: Honey. Honey 
Edith: is from time. Honey. Maple syrup. Okay. Naturally occurring. 
Robin: Yes. All right. So we've talked a little bit about how difficult this is, but at Charter Research, you think we may have something.
 You've done some trials and you've gotten a drug approved. which is no small feat. So tell me what's going on with this drug. 
Dr. Rivera: So that's, that's the latest drug that was approved, uh, a few months ago. 
Robin: Kinsula, or something like that. Yes, 
Dr. Rivera: the generic name is Donanimab [00:16:00] and, , the, commercial name is Kinsula or Kinsula, uh, or Tomato, tomato.
Kinsula. Is one of those things that difficult to pronounce, but we're going to get there. We're going to learn how to pronounce it at some point. So, yes, that's the newest one. We were a integral participant of that research is called trail blazer 2 a study that Eli Lilly. was a sponsor for and we were part of that.
 , thank God we were, able to contribute to science and contribute to our fellow citizens, , on this, on this drug. So we had a number of patients, , not only that, that were, Active participants, but we had a bigger number of patients that wanted to participate and we had to put them through the screening process and then decided they were not a good candidate.
So we still have a couple of them that are in the tail end of the study, which is the follow up part. [00:17:00] The treatment portion is over with them, but they are in the follow up part to make sure everything is fine. So we are very grateful that we were part of that. 
Edith: Is it a fair question to ask, the difference between Kinsula and Lakembi? 
Dr. Rivera: Uh, yes , it's a very, \ fair question to ask because they are both, , recently approved and they're both for the same indication and patients are going to have to, at some point decide, , do I take, Motrin or do I take Aleve?
So they're both in the same family. They're both monoclonal antibodies. , and they're both, , anti plaque, anti amyloid plaque. So they both attack the plaque. They attack the plaque at two different, , points in that, in that, uh, polymer, but uh, nonetheless is the plaque itself.
It's not the flowy portion of it. Okay. However, one is given every two weeks. The other one is given every month. 
Edith: Oh, okay. And they're both infusions? 
Dr. Rivera: They're both IV infusions. The one that is, , [00:18:00] every two weeks, the Leqembi, is about an hour infusion. And the one that is, , every month donanemab, is , about 30 minutes infusion.
Edith: Oh, okay. That's, that could be a game changer for many people, it would be for me. 
Dr. Rivera: Yeah , some patients will tell you directly, , and openly they'll, they will tell you, I'm not going to be tethered to this center, , when I'm supposed to be retired and enjoying my retirement. So 30 minutes is a good chunk of time.
Edith: Yeah. Yeah, 
Dr. Rivera: I'm not, I'm not suggesting Leqembi being one hour is bad. Understood. Right. But, , it's just the difference. All the people are saying, no, I, have all the time in the world being retired. I don't have an agenda to follow. So I can be here. And they believe that being every two weeks is hitting them harder.
And therefore their plaque goes, it's going to. clear faster. Whether that's true or not, that's a different story, but that's what they believe, and they, they will tell you, I want the other [00:19:00] one. 
Edith: Do they both have the same mechanism? Do they both clear in the same way? 
Dr. Rivera: so the answer is yes. The direct answer is yes.
, they're aimed to clear the plaque. , In theory. In practice, they don't clear the plaque at the same rate. 
Edith: Oh, okay. Okay. Big difference. Well, that's not, I shouldn't say big difference, but that's a significant difference between the two. 
Dr. Rivera: Correct. In fact, the, , the new one, Donanabab Kisumula, is, is based on the clearance of the, amyloid plaque.
In other words, they will do a PET scan first to see the extent of the amyloid burden. And then they start the treatment and then they'll do another PET scan at some point to see , if it has cleared or not or how much has cleared,, because that's going to determine the extent or the duration of the treatment, which some people clear at six months, some people clear a year.
Some [00:20:00] people clear at 18 months. The other one doesn't require that. The other one, you continue taking it and it's not based on the clearance of the plaque. Okay. It clears the plaque. That's the mechanism of action, but , they don't decide whether to stop or not based on, on the clearance. 
Edith: So you take it indefinitely.
Dr. Rivera: Correct. 
Well, let me define that. Okay. Your clinician, the doctor that he is. prescribing it will determine with other things because remember the plaque is just a physical thing in there. We call that biomarker, right? But the ultimate objective of any of these drugs is to improve your cognition.
So there's a number of other ways to find out if your cognition is improved or not. So in the one that has no pet, , criteria, then the clinician is going to decide, based on other ways, if your clinician is getting better or not. [00:21:00] And at that point, they may decide, okay, you have improved this amount, I think is enough.
So , they weight the, , benefits versus the risk. So they say, you have cleared enough and, there are some inherent risk for this drug, I don't think you should continue. So that, that's a decision that the clinician and the patient will take. 
Edith: Fair enough. So like what risks?
Dr. Rivera: So any drug, any medicine that you take, every medicine is going to give you some side effects. Some more than others. And some, more severe, 
now, the three important side effects that these type of drugs do that others don't do is one of them infusion reactions because they are infusion and they're biologic. So every time you take a biologic through the IV, you can get infusion reactions.
 Uh, and then the other two are, , Brain bleed and brain edema, swelling. Now brain bleed sounds terrible [00:22:00] because it is, but it's not brain bleed like a stroke or a hemorrhage at all. Those are little dots of blood that leak in the brain. So you mentioned before the, , Plaque that you know, which is in the teeth.
So when you're scraping that plaque out, you may have some blood showing your gums That it's not a hemorrhage, but it's a little bit of blood here and there. 
Robin: Yeah 
Yeah 
Dr. Rivera: Same thing, same thing happens here. You're scraping that plaque out chemically, not physically, but still you're scraping it out and you may have some of those little dots of blood.
What's going to show that is an MRI. The MRIs are going to be done , for both in a specific interval of time between or during the treatment. And then the third one is the edema, which is swelling, a little bit of fluid around that area. , and that's also, going to give you some, symptoms. Now the symptoms vary depending on where that bleed [00:23:00] and where that edema is in the brain and how big it is, uh, or how small. 
Edith: And not everybody experiences any of these or everyone, 
Dr. Rivera: all of them. That's the good news , anywhere between 80 and 90 percent of the people don't have any symptoms.
Woohoo! 
Edith: Yeah. 
Dr. Rivera: Yeah. 
Robin: All right. Now, this is not something you can just get a prescription for and hop down to Walgreens. 
Dr. Rivera: This, , to the drug medicines, no, no. You need a prescription, but not at Walgreens, you don't go to Walgreens for that.
So the doctors that are prescribing it. They have to be, for lack of a better term, registered, in a specific registry so that they, can prove that they, are knowledgeable with the drug. , and that they have certain infrastructure. They don't have to give the drug themselves, but many of these doctors have an infusion center in their office, which makes it much, much more convenient for the patient and easier for them to follow the patients up.
Or they may have some [00:24:00] type of arrangements with a, an infusion center, and then they'll write the prescription and send the patient to the, to that center. And what 
Robin: results are you seeing with this drug? 
Dr. Rivera: So what we have seen is, , it depends how you Cut the pie, right? Mm. So, , we have seen that at 18 months 85 percent of the people for this drug clear the plaque to the point that they didn't need the drug anymore.
Edith: Wow That's 
Robin: that's amazing 
Dr. Rivera: Hold on because remember Aduhelm, Aducanumab as we know about yeah, it was the first one in 2021 that was approved And it was approved because of that So, uh, the FDA took that as a surrogate of good effect. If it's clearing the plaque, then we assume that it's going to do well for the cognitive function. It turned out that it was not that way, [00:25:00] at least with the data that they had at the moment. So they continued gathering data and finally decided to not, not because the data was bad, but you know, they did, a cost benefit analysis and decided to take the drug, uh, out of the market. So I say that to tell you that now this 85 percent is not, uh, does not mean that the patient is going to be 85 percent better.
Right, right. 85 percent cured. By the way, none of these drugs cure the disease, right? They alter the disease, but they don't cure the disease. So that's one way of looking at it. The, clearance of the plaque. The other way, which is the real way because that's what your caregiver and yourself, you want for your life is a better cognitive function so that it can improve your quality of life.
Yeah. So for that one, , is is a little iffy because what they measure was [00:26:00] a reduction in the rate of decline. 
Robin: That's tricky. 
Dr. Rivera: Yeah. It's a little tricky. Yes. They. They measure it, but they're not, , alleging that they improve the cognitive function, 
Edith: right?
What 
Dr. Rivera: they improve is the rate of decline. So they're buying time for you. That's what they're saying. So that was about 35 percent improvement in the rate of decline. So that buys, anywhere between , four and a half months. And, 10 months of, of slowing the process.
Robin: So you would want to start this drug earlier in the disease than later. 
Dr. Rivera: Correct. Absolutely. Like everything else, uh, once it's too late, it's too late. This is a degenerative disease. And it starts getting worse and worse and worse until finally the, the cell dies.
Once the cell dies, There's not much to do. . So early on is much better. And that's the patients that have [00:27:00] seen improvement in these studies. 
Robin: That's wonderful. 
 
Robin: Thank You so much for, for explaining all of this very difficult stuff in a way that I could understand. Hopefully our listeners understood as well because it's fascinating to me. It 
Edith: is. It is. 
Robin: Yes. Yes. And if you have thought,. Well, I would like to be one of these volunteers that's helping to find a cure. You can go to charter.
com or you can call us here at ADRC and we will point you in the direction of a study. 
Dr. Rivera: Charterresearch. com. 
Robin: Charterresearch. com. Charterresearch. com. 
Edith: Otherwise, you'll end up out on the ocean. 
Robin: Yes. 
Dr. Rivera: By the way, we we need volunteers in a number of ways. , so people think, oh, I don't have the disease. You know, , I can't volunteer even if I want to.
There's a number of ways that you can volunteer and help the participants. So the volunteer participants are great, uh, but there's other ways and you may have family members or you may have friends that can, , that can be participants as well. 
Robin: Yes. It's all part of [00:28:00] finding that cure or finding that new drug is we need volunteers.
Edith: Everybody's going to have to understand that, right? We need a diverse group of volunteers. If we don't know you, we can't help you. 
Robin: Yeah. Yes. Alright, please make sure to subscribe to our podcast, Informed Aging. Tell your family and friends about us. If you'd like to support the work we do at the Alzheimer's and Dementia Resource Center, please go to ADRCcares.
org Slash Donate. You can find us at facebook. com slash informed aging. Today's episode was recorded at ADRC's podcast studio. That's it for now. We are looking forward to our next visit.