July 18, 2000
Scientists at the Alzheimer's World Congress this year began discussing the development of a vaccine for the degenerative disease. Jim Lehrer talks with Dr. Steven DeKosky, chair of the Medical and Scientific Council for the Alzheimer's Association, a national advocacy group.
The Health Unit is a partnership with the Henry J. Kaiser Family Foundation.
JIM LEHRER: Finally tonight, the latest on Alzheimer's research. Susan Dentzer of our health unit begins. The unit is a partnership with the Henry J. Kaiser Family Foundation.
SUSAN DENTZER: Roughly four million Americans suffer from the debilitating effects of Alzheimer's Disease, along with another eight million worldwide. But those numbers pale compared to the total of 22 million around the globe who could be affected by 2025. As the first international conference on Alzheimer's wrapped up today in Washington, D.C., there was both worry about the future and a glimmer of hope stemming from news of potential new treatments. Researchers from a California biotechnology company, Elan Pharmaceuticals, reported on the latest progress toward an Alzheimer's vaccine. First announced a year ago, the vaccine appears to prevent or reduce one of Alzheimer's key features, but so far only in mice and other animals. Those features are the sticky protein deposits in the brains of Alzheimer's patients that are known as amyloid plaques. The plaques are believed to cause the death of other brain cells.
SUSAN DENTZER: The scientists at Elan first genetically altered a group of mice so that they developed the exact type of plaques found in humans with Alzheimer's. Then they harnessed the animals' immune systems to fight the plaques by injecting the mice with the vaccine. That shrank or eliminated existing plaques and blocked formation of new ones. The slide on the right is from the brain of a mouse that had been given the vaccine. It had virtually no plaques, compared to the slide on the left of an untreated mouse. At the conference, the Elan researchers added the good news that the vaccine had passed the first round of safety tests in two dozen human Alzheimer's patients.
DR. DALE SCHENK, Elan Pharmaceuticals: We are just now getting into the first step, which is safety studies, and the initial results from those studies in the U.S. suggest that the vaccine was well tolerated. That means the vaccine can now move ahead to clinical trials next year to test whether it actually works to reduce plaques in humans.
|Amyloid proteins in the brain|
JIM LEHRER: More now from Dr. Steven DeKosky, head of the Department of Neurology and the Alzheimer's Center at the University of Pittsburgh Medical Center. He also chairs the medical and scientific council for the Alzheimer's Association, a national advocacy group. Doctor, welcome. Help us understand how important this vaccine development is.
DR. STEVEN DeKOSKY, University of Pittsburgh Medical Center: Well, I think there are a number of important points about the vaccine. The first is, of course, that it represents a way that we could treat, as well as try to prevent Alzheimer's Disease from developing in people. The second is that the early studies, especially in the mice, they've now been accompanied by some other studies by other groups using other techniques, how that we actually can stop or slow down the accumulation of this amyloid protein in the brains of experimental animals, which means we think we ought to be able to do it in humans.
JIM LEHRER: And that amyloid protein, that is the most crucial part of Alzheimer's, is it not?
DR. STEVEN DeKOSKY: Well, it depends on whom you ask. There are groups who feel that it is the primary and the central problem with the disease. There is another signature abnormality in the brain that occurs in all patients with AD called neurofibrillary tangles, and these are gatherings of an altered protein inside nerve cells which itself can kill the cells. The amyloid and the plaques -- the amyloid plaques and the tangles were the two things that Alzheimer, himself, noticed when he first described the disease. We think the amyloid is the starter point. We certainly believe that what happens in the brain that causes a lot of the trouble in thinking relates to amyloid, and that's why it's become a prime target to try and stop.
JIM LEHRER: But the vaccine has no effect, at least no demonstrated effect on the second, on the tangles at this point, correct?
DR. STEVEN DeKOSKY: Well, the mouse models that we have right now don't have tangles. And they are models of the accumulation of amyloid -- still an immensely power and immensely useful tool. We don't know what the relationship is to tangles and plaques in the brains of humans. One of the questions will be: If you stop the amyloid, will that somehow stop the plaques from occurring, because they're somehow being started by the same mechanism, or will the tangles continue on?
JIM LEHRER: Yeah. Go ahead. Sorry.
DR. STEVEN DeKOSKY: The advantage is, here's how we look at it: People say, "Well, if you top the amyloid but don't stop the tangles, will the disease go on?" And the answer is, it's possible that it will, but when we talk about stopping amyloid to slow the progression of the disease down, if the tangles continue the progression of the disease but at a greatly slowed pace, we'll have won a great victory.
|Where does the vaccine come from?|
JIM LEHRER: Now, the vaccine, where does it come from? Is it manmade, or does it come from some natural product or what?
DR. STEVEN DeKOSKY: The vaccine is a combination of the actual bad player in the brain, the actual what we call "beta-amyloid fragment" accompanied by an immune system stimulant. So in Alzheimer's Disease, what we think causes the plaque or the deposition of this material is that a normal protein that normally is cut in quite a long place, kind of like a grass clipping, gets clipped in an abnormal place as a very, very small fragment, and it's this fragment that builds up. What the Elan people did was actually inject that fragment, we know exactly what the sequence of the protein is that makes up this little fragment, they injected that into the mice, and the mice made antibodies to it, just as you and I make antibodies when we're injected with a vaccine for pneumonia or for chicken pox.
JIM LEHRER: So if this turns out to be effective, and you'd have to go -- I'll get to that question in a minute. The next step, what has been established now with this 24 people who were given this test is that it's safe. In other words, there are no side effects that would keep a human being from taking it. Correct?
DR. STEVEN DeKOSKY: That's partly true. The humans who got it in the United States got a single shot of the vaccine. And the report was they had no ill effects. That's very good news. This vaccine, like most vaccines we're familiar with, would be given in repeated doses like booster shots, and in fact, the mice who got the treatment that they showed last year received shots every several weeks. The question is then, not only is a single shot of the vaccine safe, but are repeated shots safe, or would you have a problem that might build up over time. To answer that question, the scientists in the United Kingdom, Elan, are giving repeated injections, every two months or so, to another 80 or so patients to see if they will be tolerant of multiple injections of the vaccine. If those studies prove safe, and they'll probably be done I suspect by the end of 2000, then they will begin the treatment trials to see about efficacy or about effect of slowing progression.
|Testing the vaccine on humans|
JIM LEHRER: That treatment trial, explain in simple terms what a treatment trial of this magnitude, of this disease, with this vaccine would involve.
DR. STEVEN DeKOSKY: Well, I couldn't speculate on exactly how Elan would do it, but in general, what, what an example design would be would be a group of people who would receive repeated injection let's say once every three...
JIM LEHRER: Hundreds of people, thousands of people?
DR. STEVEN DeKOSKY: It would depend on how strong an effect they thought they would get. The stronger the effect, the fewer people you need to show your effect. But I would suspect probably a couple of hundred people to start. And then a certain percentage of those people would receive the vaccine, and a certain number would receive an inactive injection.
JIM LEHRER: And these would be people who have already been diagnosed with Alzheimer's?
DR. STEVEN DeKOSKY: Absolutely. You would want people who had as secure a diagnosis of Alzheimer's as possible, because amyloid doesn't appear to play a role in any other dementia.
JIM LEHRER: So the test would be if you could reduce the plaque, right, and if you could do that, then you're working on not only a vaccine, but you're also working on a cure, are you not?
DR. STEVEN DeKOSKY: Other way around. Actually, it's even easier.
JIM LEHRER: All right.
DR. STEVEN DeKOSKY: If it reduces the plaque, I'd say fine, but what we'll be looking for clinically in these people is whether or not the rate of change in their memory or their thinking function is slowed down. So we actually don't have a way to measure the amount of plaque in a living human now, a number of people are trying to figure that out. We're really interested in will their memories be better or will their loss be slowed.
JIM LEHRER: It's the symptoms. It's not what is going on inside. It's what you can actually see and hear and observe.
DR. STEVEN DeKOSKY: Right. At the meeting, at the world Alzheimer's Conference, which was the Alzheimer's Association's Conference last week, there were a couple groups that showed in animal models similar to the Elan model that for the first time they had some behavioral changes in the animals, the animals behavior appeared a bit better if they also were deprived of the amyloid by the vaccine. That's the first behavioral data we've seen. We were very happy to see that. The human studies would have gone on even if the mice had not shown a behavioral change, but the fact they were better the vaccine certainly is encouraging in terms of our looking for behavioral changes in humans who get the vaccine.
|Current treatments of the disease|
JIM LEHRER: Doctor, finally, there are millions of people who either have Alzheimer's who have loved ones who have Alzheimer's; everybody has the fear that they are going to get Alzheimer's. What can you tell them tonight in terms of a potential timetable, not predict whether or not this is going to work or not, but let's say it does work, what kind of timetable are we looking at for when it might be available for everybody?
DR. STEVEN DeKOSKY: Well, there are, we'll step back and do that in sequence. There are medications currently available for Alzheimer's Disease treatment -- both for the thinking problems and for the behavioral problems, and that's very important for people to realize.
JIM LEHRER: Already.
DR. STEVEN DeKOSKY: Already. That's correct. There are also supports from the Alzheimer's associations and other groups.
JIM LEHRER: Sure.
DR. STEVEN DeKOSKY: There are other medications, and some of them had preliminary data presented at this meeting, that work in different ways, but have shown some promise in treatment of the disease. And finally, the other kind of therapeutic approach to amyloid, stopping the biochemical scissors that clips it in the wrong place, was shown at this meeting. Studies of those kinds of medications, as well as the vaccines, are probably, assuming that the studies were realistically probably maybe three years away.
JIM LEHRER: Three years away?
DR. STEVEN DeKOSKY: That's my estimate.
JIM LEHRER: Go ahead.
DR. STEVEN DeKOSKY: It will take us a year to finish the safety studies of the vaccine. It will probably take another year or so for the first studies to show whether or not using the vaccine repeatedly in people slows the progression of the disease to the point where the FDA would say, okay, this is an appropriate drug to use or an appropriate strategy.
JIM LEHRER: Got you, doctor. Thank you very much.
DR. STEVEN DeKOSKY: You're welcome.