Doctor Paul Winner, DO, FAAN, Neurologist, talks about how researchers are testing an investigational drug for people with mild to moderate Alzheimer’s disease.
Interview conducted by Ivanhoe Broadcast News in February 2022.
Tell me about this drug and this study.
DOCTOR WINNER: Well, the LIFT-AD study is revolutionary in its concept. We’re trying to get to the point where we have medications that are capable of providing cognitive benefit with the potential to be disease modifying. We’d like a medicine that someone can take at home. This is a medicine that begins to solve those problems. Another thing we want to do is get a medicine that crosses the blood brain barrier easily, a small molecule. So, this is a small molecule medication that we’re trying to show can slow and potentially stop the degeneration of the brain and also help improve cognitive function. This medicine works on a naturally occurring specific neurotrophic system, the HGF/MET system. That system allows for basically maintenance, restoring, repairing and improving brain function. It improves the health of the nerve cell. It also helps to prevent the inflammation that occurs in the brain through promoting anti-inflammatory responses while diminishing inflammatory responses. So, it has that modulating effect. It also basically helps regarding improving synaptic function, which is important for how nerve cells communicate with each other. So, it has the potential to have multiple beneficial downstream effects. It’s something you could take at home once a day subcutaneously. So, that’s a huge advantage.
Why is that so revolutionary? Something they can take at home and subcutaneously?
DOCTOR WINNER: Well, so far, we’ve had symptomatic treatments which have primarily been oral. They really don’t change the disease process. Lately in research, we’ve been using antibody therapies to remove amyloid or tau, and they are showing us some benefit. For antibody therapies, a patient has to come to a center like ours and have an infusion, an I.V. infusion. They’re here for hours. So that is inconvenient. These IV infusions are difficult for many patients, even here where we have good weather but even more so when we have bad weather. Additionally, the pandemic has posed huge challenges for this patient population, making it difficult for patients to get their medicine. A take-home therapy helps to empower patients and their caregivers while addressing their mild to moderate Alzheimer’s in the comfort of their home, rather than having to deal with the many challenges associated with I.V. infusions.
What is the need for something like this?
DOCTOR WINNER: There is a definite need to have medications for Alzheimer’s disease dementia. About one in three elderly adults will die from dementia. The effect of dementia on a family, on everyone around an individual with dementia, is unbelievable. It’s not just the patient who is suffering. In fact, sometimes in the later parts of the illness, the patient doesn’t even realize what’s going on. The family member, the caregivers, everyone around them is suffering so much because of this disorder. There is a great need right now for us to control this disorder. So many people are dying from this. Dementia has a huge impact on society in every way possible. I’m not even touching the monetary issues that this disease has on families and society. So, we need to develop more therapies that address cognitive performance with the potential to modify the disease course. These are therapies that will slow or alter the progression of this disease. So, that’s what we’re looking at with many developing medications. I do not see (as Dr. Winner speaking personally) that we are going to find a single treatment. I think disease modification will require multiple medicines working in multiple sequences to eventually see meaningful changes in those with dementia. See, Alzheimer’s is complicated. It’s not one disorder as we look at it. There’re aspects of tau, there’s aspects of amyloid and it’s very complicated. The amyloid begins to form something called A-beta 42 an abnormal formation. It’s a soluble component when it becomes an oligomer and that starts to essentially clump, and that starts to damage cells. That ultimately leads to what we call plaques, and people are somewhat familiar with amyloid plaques.. That also starts a process of damaging the cell in a way with tau, basically a superstructure, a framework inside the nerve cell that holds it together that starts to get phosphorylated resulting in further damaged. Ultimately what happens is the cell starts to fall apart, and that’s when things start to really get very bad with progressive regarding decline of neurologic function. It’s no longer just forgetting. In the beginning, it’s mostly forgetting and short term memory loss, but later it affects every aspect of neurologic function. I foresee in the future that, depending on the time that we make the diagnosis and the person’s stage of disease, we will use different medicines at different times. See, the sinister thing about Alzheimer’s disease and some of these other dementias is that they start 20 years before the person even knows they’re sick. We need to get in front of this. We can today with many of our testing techniques. We surely can get in front of it five and 10 years. Right now, we still need to make very accurate diagnoses when people walk in the door. Like I had a person just a few minutes ago. They realize they’re forgetting. They go to the store, don’t remember why they’re there, and then they get home and say, ‘Oh. Sheesh. I forgot this item.’ Occasionally that can happen to somebody. But this is happening every day. This is happening every week. Family comes over. They have discussions. They get a phone call that night. So, what did you think about what we talked about today? What did we talk about today? Were you here? I mean, this is devastating to the patient, but it’s devastating also to the family, and in the beginning, they know. This patient absolutely knows something’s wrong and there is something wrong. So, when you start off with a correct diagnosis. You must get the right diagnosis. You must figure out is this mild cognitive impairment pre-Alzheimer’s? Is this normal aging, what I call the worried well? These are people that as we get older, it’s a little harder to learn things.
You’re going to make me call my doctor when I get home today. I’m completely paranoid. Tell me about the results you’re seeing in this study so far.
DOCTOR WINNER: Well, so far it is early. I can tell you it’s a double-blind placebo-controlled study. What that means is the doctors and the patients do not know. Patients are given 40 mg, 70 mg or a placebo in a one to one to one ratio. So, there’s basically two thirds chance of getting the active medicine. We are already seeing patients respond in a clinical way, I can’t say what dose they’re on but we are seeing responses. That’s a very positive thing, having done research for over 20 years.
That’s awesome. This study is being done not only here, but I saw something from Portland.
DOCTOR WINNER: Yeah, the study is taking place at around 50 different locations across the United States. For more information, visit https://www.lift-adtrial.com/
Who funded this study?
DOCTOR WINNER: Athira is the pharmaceutical company who discovered this and who is funding the research for this product, and it’s called ATH-1017,. ATH-1017 is a small molecule, which means it can get into the brain and work efficiently, and that’s what we’re testing, how quickly it works, how effective it is, basically to stop the degeneration of the brain and to help improve cognitive function.
Are you directly or indirectly compensated by the manufacturer for the involvement with this procedure with this drug?
DOCTOR WINNER: Athira does fund this research, and they do pay for the research that we do on this product all under FDA guidance.
Would you use this product, procedure, drug or do this study if you weren’t compensated?
WINNER: This is so important, the answer is yes because as I said earlier, we need to find more than one treatment algorithm. This is very exciting because it does work in a different pathway. It is not removing amyloid. It is not removing tau, and they’re important, and we’re going to need those. We also need to be able to get the nerve cell to stay healthy. We need the nerve cell to function better, and that’s what this product is doing. It’s working in a slightly different area. We know there’s inflammation. This is working to decrease inflammation. So, these are key aspects in this whole framework of how Alzheimer’s takes place in the brain. So, this has enormous ramifications and could possibly be used at other stages of the disease beyond the mild to moderate Alzheimer’s population.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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