Ronald Petersen, MD, PhD, on the State of Care of Alzheimer Disease

March 9, 2019

The director of the Mayo Clinic Alzheimer Disease Research Center and Mayo Clinic Study of Aging spoke about the current therapeutic landscape of Alzheimer disease, among other topics.

Ronald Petersen, MD, PhD

To Ronald Petersen, MD, PhD, one of the greatest challenges right now in the space of Alzheimer disease is participation in recruitment of clinical trials.

Petersen stresses the importance of clinicians enrolling patients in these trials to uncover new therapies, and while there are symptomatic therapies available, they do not have an effect on the long-term outcome, which is why Petersen and colleagues are hopeful that the field is headed toward the development of disease-modifying therapies

The director of the Mayo Clinic Alzheimer Disease Research Center and Mayo Clinic Study of Aging, spoke with NeurologyLive in an interview to dive deeper into the current therapeutic landscape of Alzheimer disease, among several other topics.

NeurologyLive: What’s the current therapeutic landscape of the Alzheimer disease?

Right now in Alzheimer disease from a pharmacologic perspective, we have 4 or so symptomatic drugs on the market, I mean these are drugs thought to ameliorate some of the symptoms of Alzheimer disease and 3 of them are in one drug class called acetylcholinesterase inhibitors and they’re meant to increase the activity of the neurotransmitter acetylcholine in the brain, and that's involved with memory, thinking, behavior and the like, so the drugs are meant to keep the amount of that chemical available active longer in the brain. Then there's a fourth drug, a different class, called an NMDA antagonist and this drug, memantine, works on a different chemical system in the brain, a glutamate system, and also sort of modulates its activity.

All of these are again symptomatic treating drugs and what we do not have in the field and where the field is headed we hope, is toward the development of disease-modifying therapies, so these would be therapies that would be designed to get at the underlying cause of the disease namely plaques and tangles, the plaques are made of a protein called amyloid, the tangles are made of protein called tau, and so there are several drug trials underway right now that are aimed at getting at those 2 proteins and trying to remove them from the brain. Clinical trials is a big area of activity in the Alzheimer field right now since we need those drugs to really make a difference in the ultimate outcome of patients over time.

The symptomatic drugs that I discussed earlier really do not have any effect on the long-term outcome, do not extend life or anything of that nature, and while they may improve symptoms, they are basically not thought to do anything with the underlying disease process. We are using those drugs for symptomatic treatments because that's what we have right now, but we're clearly focusing on developing these new therapies that are going to be disease modifying.

Are there any challenges or areas of unmet need that you've noticed?

Well, the big one is participation in recruitment for clinical trials. We still are in the phase where people don't think about getting into a research trial for a new drug like people would with cancer, if you have a cancer that's difficult to treat you would go to an academic medical institution and say what clinical trials do you have for this kind of cancer. People tend not to think about that very much with Alzheimer disease but we need to, so both the general public, the patients, the families, as well as the doctors should be thinking about putting people into clinical trials because that's the only way we're going to really make headway in trying to uncover some of these therapies for Alzheimer use.

This is a big plea to practicing physicians to have you and your patients consider participation in clinical trials.

Is there any clinical trial that you're watching closely?

One, in particular, that’s nearing completion is with an antibody called aducanumab (Biogen), an antibody that is injected into the bloodstream and is thought to go into the brain and remove the amyloid from the brain, and the preliminary studies have indicated that it, in fact, does that when you measure the amount of amyloid in the brain with PET scans.

Are there any misconceptions that you think need to be addressed?

Well, I think in the general public and hopefully not in physicians, that Alzheimer disease is sort of a part of normal aging, well geez don't we all get forgetful as we get older? The answer to that is yes, a little bit, but Alzheimer disease is an abnormal protein problem in the brain, and it is a disease. I think we have to avoid ageism if you will, and say well he's old what do you expect because these conditions may very well be treatable.

What are your thoughts on the amyloid hypothesis?

I think amyloid is definitely a player in the Alzheimer disease process. More recently people have been talking about it as a defining feature that Alzheimer disease is defined by the presence of amyloid and tau in the brain and if that’s it, then that’s it.

Amyloid I think is a major player, but I don't think it's the whole answer by any means or that even treating amyloid MISS 709 processing adequately would eliminate or erase the disease; I think it would have an impact on the disease but I think ultimately we're going to need combination therapy, so treating amyloid, maybe treating tau and other factors along the way. It is a player and its role may vary with the age of the person and stage of the disease, that is amyloid may be very important early on in the disease process and become perhaps less important as a person ages, so the complicating factors.

What are the value of biomarkers?

If you define Alzheimer disease by the presence of amyloid and tau in the brain, you're going to need biomarkers to detect those 2 proteins in the brain and now we can do that in the spinal fluid with lumbar punctures, where we can detect amyloid and tau, and we can do it now with PET scanning. We can do an amyloid PET scan that will identify whether the person has amyloid in the brain and we can do a tau PET scan that defines where the person has tau in the brain, so if you have a positive scan on both of those then you have Alzheimer disease by definition, irrespective of your clinical symptoms. You could be clinically normal, but if you have evidence of amyloid and tau in the brain then the new framework proposal is saying that you have Alzheimer disease, so the biomarkers are critically important and you can imagine for a clinical trial you need to have the presence of the biomarkers so that you can determine if in fact, the person has the target in the brain that the drug is aiming at namely amyloid or tau.

What's your best advice for clinicians treating this patient population?

Be sensitive to early presentations because ultimately, I think intervening on these diseases earlier rather than later is going to be the best approach. When people come in complaining of forgetfulness, not that all forgetfulness is Alzheimer disease, and not that forgetfulness is not common in aging, but trying to sort out the forgetfulness, might, in fact, be meaningful and could be the beginning of a degenerative process in the brain. So clinically being sensitive to the early features and then following the literature and the studies again with regard to the use of biomarkers, when are biomarkers going to be important in a given individual patient, and then hopefully again, with the clinical trials, that we will be able to get people to enroll in clinical trials so that we will develop some effective therapies.

When we're talking about patients and what we can do for them, lifestyle factors can be important as well, and by lifestyle we mean physical exercise, intellectual activity, social activities, things like that, so don't ignore lifestyle factors that can influence perhaps the course, maybe not prevent Alzheimer disease but certainly can alter the course.

Transcript has been edited for clarity.

Disclosure: Ronald Petersen, MD, PhD,

is a paid consultant for Biogen.