Reprinted for educational Alzheimer's scholar information purpose only, original publication and video can be found here
Transcript (Accompanied by in-text comments by Alexei Koudinov, MD, PhD, DrSci)
GWEN IFILL: Now: the latest on the search for treating Alzheimer's disease.
Judy Woodruff has the story.
JUDY WOODRUFF: The effort to develop a treatment for Alzheimer's suffered a blow yesterday when a clinical trial was halted after finding that a new drug did more harm than good. Manufacturer Eli Lilly called off the studies after data showed the drug led to a greater risk of skin cancer and more memory loss.
The setback comes on the heels of some promising news about early diagnosis of Alzheimer's. Last week, samples of spinal fluid were found to be highly accurate at predicting a patient's likelihood of eventually developing the disease. Researchers also believe that brain scans may lead to diagnosis before symptoms develop.
And to help explain the findings, we turn to a leading researcher, Dr. Paul Aisen of the University of California, San Diego, School of Medicine. For the record, Dr. Aisen was involved in the early stages of that Eli Lilly trial, and he has consulted for Lilly and several other pharmaceutical companies.
Dr. Aisen, thank you for being with us.
DR. PAUL AISEN, University of California, San Diego, School of Medicine: Thank you.
JUDY WOODRUFF: First of all, tell us a little bit more about that drug involved in these clinical trials. What was it designed to do?
DR. PAUL AISEN: Well, we think that the cause of Alzheimer's disease is a -- is the accumulation of a toxic fragment called amyloid peptide, and this drug was designed to prevent that fragment from being released and from accumulating.
Dr. Alexei Koudinov: Well, Dr. Aisen, may I ask you to talk for yourself, and avoid using "we". We means who? You, Dr.Selkoe, other shareholders of a related BioTech Stock, PIs of NIH and other Funding Bodies research grants on amyloid, or your fellow participants of NIH State-of-the-Science Conference Preventing Alzheimer's Disease 2010? Would it be practical for you to think differently, Dr. Aisen? Be specific! I and many other researchers do not think that amyloid beta causes Alzheiemer's, and we did not grant you the privelege to talk on our behalf.
JUDY WOODRUFF: And what went wrong?
DR. PAUL AISEN: Well, this was a large treatment study, with thousands of participants. And, in such a program, you follow the data. You have an independent group monitoring the trial and monitoring the data, both for safety and for impact of drug on memory. And this monitoring led to the conclusion that the drug was carrying a risk, a risk of skin cancer, and wasn't improving memory. So, that means that this dose of this particular drug is not effective at this stage of disease.
Dr. Alexei Koudinov: You are wrong! This means the whole concept and amyloid theory is wrong, Dr.Aisen! You know that, don't you?
JUDY WOODRUFF: And you said not improving memory. Is it also the case that it was making memory and other symptoms worse?
DR. PAUL AISEN: Yes. The interim analysis, the look at the data, suggested that people taking the drug had more difficulty with memory than the people on placebo.
JUDY WOODRUFF: So, now, as I understand it, this trial was at least a decade in the making. How much of a setback is that?
DR. PAUL AISEN: It's a big setback, because there are only a few drugs that are at this pivotal stage, this final stage of drug development. So, having one of the major trials fail is a significant setback for the field.
But I think the good news is that there are dozens of other drugs at earlier phases of development, and that the tools available to study and prove efficacy for these drugs are improving -- that is, the field has developed new methods that should increase the likelihood that some of these drug programs will succeed.
Dr. Alexei Koudinov: It's a major advance, Dr. Aisen! It's happened a number of years ago, Elan trial collapsed, do you remember? It should happened again, so, it happened this August 2010 with Lilly trial. it will happen again to prove simple truth: amyloid is not an enemy, amyloid beta protein is a friend of the diseased brain, aiding the function, impaired by the other primary disease cause. So, you simply can not remove it from the brain!
JUDY WOODRUFF: So, then those other trials are -- are continuing.
Meantime, as we reported a moment ago, there are some promising new developments with regard to diagnosing Alzheimer's. Tell us a little bit more about that.
DR. PAUL AISEN: Sure. The -- the basic abnormality in the Alzheimer's disease brain is, as I said, the accumulation of a toxic fragment called amyloid. And we have always been able to be sure that Alzheimer's is present after death when we can examine brain tissue and see the amyloid in brain.
Now, for the first time, we can very accurately track the accumulation of amyloid with tests in living people. We have two tests, a PET scan, a form of brain scanning, and sampling of spinal fluid, that now give a very accurate indication of amyloid buildup in brain. This is a major step forward. It allows us to identify people well before dementia has occurred, even before memory impairment has occurred.
Dr. Alexei Koudinov: Why you are not mentioning amyloid accumulation in other human brain disease states, as well is amyloid accumulation in non-demented individuals?
JUDY WOODRUFF: So, earlier diagnosis, but the question is, if you don't have a treatment yet, what good does that do?
DR. PAUL AISEN: Well, the major benefit of these advances is that it gives us a tool for drug development.
Right now, these are research tools primarily. They will allow investigators to identify people before symptoms have occurred or before symptoms are bad, at the early stage, at which the disease is likely to be treatable, identify people at this stage, and test their drugs at this stage.
So, the trial that was just stopped was conducted in the dementia stage. It may well be that the dementia stage is too late for such a drug to work. We now know that amyloid accumulates 10 or 15 years before dementia. And we think that, for anti-amyloid drugs to be effective, the earlier the better we intervene.
These tools give us a way of testing the drugs at the earliest stage, and ultimately can be used -- when we prove that these drugs work, they can be used to guide therapy in people before the onset of symptoms (AK: see related article by Dr.Aisen).
Dr. Alexei Koudinov: Well, one faked tool we have for more then a decade, a so called Gold standard for testing Alzheiemr's therapies. You know what I am talking about, right? A so called Alzheimer's transgenic mouse. No wonder, assisted by faked peer review at Nature, amyloid mafia got a ticket for testing drugs in Humans.
JUDY WOODRUFF: Having said that, Alzheimer's was identified, I was reading today, in 1906, so it's been over a century. Why is this such a tough disease to make progress on?
DR. PAUL AISEN: Well, first, this is a disease that can't be directly observed.
So, if you're testing a drug for blood pressure, you measure blood pressure, you get a quick answer. If you're treating a rash, you can watch the benefits of the drug. In Alzheimer's disease, this is not a -- it's not a condition that's apparent.
We have to use indirect measures of the disease. And that creates a lot of noise, a lot of measurement difficulty. Up until now, we have relied on memory tests and similar assessments. But they're not very accurate. Memory fluctuates from day to day. It's not a very precise gauge of disease progression or the impact of drug treatment.
Now we have new, much more precise measures of disease that allow us to identify people at the very early stages, as we said, but also to much more precisely measure the impact of treatment. So, I think that clinical trial methodology has advanced, and that's going to help us demonstrate effective treatments.
Dr. Alexei Koudinov: You know, what I got in mind is a Russian (Soviets-time) anecdote of a TV appearence of a Big Professor (just like you at PBC this time) reporting the Tooth Extraction over anus. So much amazed TV reporter is asking "why" and "what for"? ...and the answer is straight forward and cristal clear: First, because all we do we do this way, and Second, because (for tooth extraction) it is for the first time ever. So, Dr.Aisen, don't oversimplify the story. As you are on the wrong pass with Alzheimer's theory, no methodology will yield the cure. Period!
JUDY WOODRUFF: Dr. Paul Aisen, we're going to leave it there. Thank you very much for talking with us.
DR. PAUL AISEN: Thank you.
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