AN ALZHEIMER'S VACCINE?

July 8, 1999
		A recent study found a vaccine that could be used to treat and even prevent Alzheimer's. Margaret Warner talks with Dr. Steven DeKosky, head of the Alzheimer's Disease Research Center at the University Of Pittsburgh. Dr. DeKosky also takes your questions in an Online Forum. The Health Unit is a partnership with the Henry J. Kaiser Family Foundation.

Forum: Dr. DeKosky takes your questions. Remaking Medicare June 24, 1999: Should doctors unionize? June 7, 1999: Mental Health Conference May 27, 1999: A Choice on Heart Disease Jan. 27, 1999: Treating Parkinson's Disease. Jan. 4, 1999: Long-term care. Oct. 30, 1998: Multiplying brain cells. March 12, 1997: Alzheimers findings The NewsHour's Health Spotlight. Browse the NewsHour's coverage of Health   Alzheimer's Association. Elan Corporation Statement Nature	SUSAN DENTZER: Roughly four million Americans suffer from the debilitating effects of Alzheimer's Disease and almost nineteen million say a family member is affected. Among the afflicted are former President Ronald Reagan and as many as half of the residents of the nation's nursing homes. The longer people live, in fact, the more likely they are to have Alzheimer's. While one in ten persons over 65 have the disease, by age 85, nearly half do.
	Halting the disease's progression
	SUSAN DENTZER: Recently a handful of new treatments have shown some ability to stem the memory loss and other mental deterioration that patients undergo. And in this week's issue of the journal "Nature," researchers from a California biotechnology company reported on a vaccine that kindled new hopes. The team from Elan Pharmaceuticals said it had developed a vaccine for use in mice that appeared to prevent or reduce one of Alzheimer's key features. These 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. DR. IVAN LIEBERBURG, Elan Pharmaceuticals: This drug completely stopped all further progression of the disease and, in some cases, actually lessened it. 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, in what yielded the key breakthrough, they harnessed the animals' own immune systems to fight the plaques by injecting the mice with a specially developed vaccine. The vaccine appeared to shrink or eliminate existing brain plaques and to block 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 plaque deposits compared to the slide on the left of an untreated mouse. Elan now plans to ask the federal Food and Drug Administration for authority to begin testing it on people later this year.
	A discussion on the scientists' findings
	JIM LEHRER: And to Margaret Warner. MARGARET WARNER: Joining me now is Dr. Steven DeKosky, head of the Alzheimer's Disease Research Center at the University of Pittsburgh. He's also chairman of the Scientific and Medical Advisory Board of the Alzheimer's Association, a national advocacy group. Welcome, Dr. DeKosky. How significant do you, in your view, is this finding reported today? DR. STEVEN DE KOSKY, Alzheimer's Association: We think, both the researchers in the Alzheimer's community and the association, that this is a striking finding. It was a bit surprising, I think, even to the scientists who did the study themselves. I don't think they thought it would be as effective as it turned out to be. MARGARET WARNER: And what -- without being maybe too technical or medical with us -- what is significant about it? What's the big breakthrough that you see? DR. STEVEN DE KOSKY: They did two experiments that they reported in this paper. They first gave their vaccine to animals who we know will develop the sticky plaques in their brains, the little deposits of protein in their brains, as they get older. Then they started giving these animals the vaccine before they developed the plaques, and, in fact, when they looked at them a year later, when their brains should have been full of plaques, they had none, and they did not have any of the other inflammation or negative effects that accompanied the formation of this material in the brain. They had basically prevented them from developing the changes. The second experiment they did was on animals in whom they waited until they were old enough to already have plaques and gave them the vaccine then and continued to give it for several months, and those animals not only stopped developing more plaques, but it was pretty clear that they also began to resorb the material that was in the brain, that is, they were improving. MARGARET WARNER: Okay. Now, in humans, first of all, do all Alzheimer's patients have these plaques? DR. STEVEN DE KOSKY: Yes, all Alzheimer's patients do. In fact, that's one of the criteria, one of the ways we make the diagnosis of Alzheimer's Disease. If there aren't plaques in the brain, it's probably some other neurological disease. MARGARET WARNER: And what is known about whether these plaques are a symptom, just a symptom of the disease, or cause the disease? DR. STEVEN DE KOSKY: We know that the plaques are made up of a material called amyloid. In some families, who have familial Alzheimer's Disease, they have a mistake, a mutation in the protein itself. And those people all get Alzheimer's Disease. So we know that if you have a problem with this protein, you will get the disease. That's a very small number of people. It's only probably 10 families that we've identified, but it proves that this protein is clearly involved in the cause of the disease in those patients and in the disease process in everybody else who gets the disease.
	Combating other abnormalities
	MARGARET WARNER: But there are also -- without going into great detail -- but there are other abnormalities in the brain characteristic of Alzheimer's patients, correct? DR. STEVEN DE KOSKY: Absolutely. MARGARET WARNER: That aren't addressed by this vaccine. DR. STEVEN DE KOSKY: That's correct. I think you can -- we have two major types of changes in the brain that occur in Alzheimer's Disease. One is these deposits of the protein called amyloid, and the other is deposits of a different kind of protein that occur inside the nerve cell. This vaccine and this strategy only attacks the amyloid plaque portion of the pathology. Now, if you say, well, what does that mean as far as patients are concerned, that's the whole question. We want to know, we need to know if we find an effective way to slow down these deposits in the brain will that slow down or stop the whole process, or will the process continue and let us just see no change in the course of the disease in patients. I think most people who study the disease believe that if we are able to slow this half of the problem down, that what we would see in patients is a slowing of the progression of their disease. MARGARET WARNER: All right. Now, often, I gather, experiments in mice don't translate to humans. Is there anything here that gives you special hope or reason to think that this might? DR. STEVEN DE KOSKY: Right. It's appropriate always to be cautious, and, in fact, I think we need to re-emphasize that this is not a cure for the disease; this is what we hope will be a good treatment and possibly a prevention. But the studies in Alzheimer's Disease which have been done on mice up till now have all been done not on models of Alzheimer's Disease, per se, but just on mice that are very old because they develop some memory problems, and you can treat them with various medicines that improve their memory. That's not the same kind of change you see in the brains of Alzheimer's patients; they lose many more of the connections in their brains than mice do that get old. These mice have the human protein put into them; they're carrying the human protein. And it was the human protein that was used to vaccinate them with. So it was a human protein that they are responding to, and it's human protein that they're clearing out of their brains. That's the reason why we think these have much more applicability to humans than did some of the earlier studies that were just looking at aging changes in mice brains.
	The clinical trial timetable
	MARGARET WARNER: Okay. Now, if the FDA approves the beginning of clinical trials in this, how long are we looking at? First of all, how long will the trials take, and if people want to be in the trials, how do they get in them? DR. STEVEN DE KOSKY: Okay. I suspect that the first trial -- what the Food & Drug Administration calls Phase 1 trials -- to make sure that the vaccination is safe -- probably would begin within a year, because I believe the company has data that suggest that they have some safety data. Certainly, the mice were reported to have done well and not had any ill effects of the vaccine. They need to show that in another species of animal and then they can try it in humans for safety. Then it will take a study probably of several hundred people being given the vaccine and tested in their thinking function and memory function over the course of a year or so before we'll know whether or not it is effective in slowing the progression of the disease. And in order to do that, we first need to make sure that when humans get the vaccine, they have a good response of making antibodies to it, just as we want people to make antibodies to vaccines we give them for the flu. MARGARET WARNER: So, the lead time between any experiment like this in mice and a drug widely available on the market is how many years, even if it works? DR. STEVEN DE KOSKY: Well, if it works, depending on what the FDA says about it, this is something that realistically could be -- I would say an aggressive timetable would be four years to five years. MARGARET WARNER: And is it fair to say that with the aging of the baby boomer generation, if we don't get a handle on this, we're going to have a lot more cases of Alzheimer's in the next -- the next 10 years? DR. STEVEN DE KOSKY: This is why, I think, most of the researchers and the association feel that we're in a race. We have discussions about whether currently there are three million or four million cases of Alzheimer's now in the U.S. What everyone knows is, that over the next twenty to thirty years we are probably going to triple the number of cases that we have. This is enough to break Medicare all by itself, so we're in a bit of a race against time to find a way to slow the progression of the disease, or to figure out a way to stop people from developing the disease before it really gets started. And that's why the first study that they did, trying to stop the deposition of protein in the brain was so exciting. It looks like we could treat people and stop them from developing the plaques before they start. MARGARET WARNER: All right. Well, thanks, Dr. DeKosky, very much. DR. STEVEN DE KOSKY: Thank you.