What We Learned

There are numerous clinical trials currently underway attempting to either improve the symptoms (memory, activities of daily living, orientation) of patients with Alzheimer’s or to slow down the progression of the disease. A recent visit to the Web site www.clinicaltrials.gov pulled up reports of 533 studies either getting underway or recently completed. This number alone should be extremely encouraging to those patients and their families desperately in need of help. Efforts to find an effective therapy are in high gear, and many new ideas wait their turn in line.

At the recent Alzheimer’s Association International Conference on Alzheimer’s Disease (ICAD) in Chicago (July 2008), Dr. Robert Green from Boston University reported that one such trial, using a drug called Flurizan, failed to show any impact on the rate of progression of Alzheimer’s disease when tested over an 18 month period. From my perspective, this was a very impressive study. About 1,600 patients were enrolled in the trial at over 120 centers around the country. A clear decline in performance was seen in this patient population over the 18 months, exactly as I expected. When comparing the results from the drug-treated patients with those who received the placebo (a tablet containing no drug), there was no difference at all. The results from the various groups (more than one dose of Flurizan was tested) were virtually identical. So why would I be so impressed by a study which showed clearly that the drug did nothing?

The major reason is that it did prove possible to manage a large scale clinical trial of this type and to obtain high quality results when testing a drug in over 1,600 patients at centers around the country. If Flurizan had shown even a quite small effect on the rate of decline in Alzheimer’s disease, it would have been seen in this study. This is very good news: when we find the right drug, we’ll know it, if we carry out studies with the same high degree of care and attention to detail. There has been a great deal of debate about whether such a trial was manageable, and concerns about the variability between different patients and in the way patients are handled at the different centers. The Flurizan trial put my mind at ease: we do have the ability to test drugs in a rigorous fashion, and to get clear answers about what is and is not worth pursuing.

Of course, I too am disappointed that Flurizan did not yield positive results, but there were good reasons to doubt that it would from the start. Again, from a personal perspective, I did not expect to see positive results from this trial. Does that mean I think the study should not have been done? NO! Until we have a full understanding of the biology of Alzheimer’s disease, there will be many different ideas which will be tested in clinical trials, and we really need to do well designed trials to find out what works and what does not. Most will not work out, but we won’t know that until we do the study. I remain confident and excited that the day is coming when we will see a truly effective treatment for this disease.

Dr. Davies, Ph.D., received a B.Sc. and a Ph.D., both in Biochemistry from the University of Leeds, England. He was a post-doctoral fellow in the Department of Pharmacology at the University of Edinburgh, Scotland before joining the staff of the Medical Research Council Brain Metabolism Unit in Edinburgh in 1974, where he began his research on Alzheimer’s disease. His first paper on cholinergic deficits was published in 1976, and followed by a series of papers in this area. This work was instrumental in the development of the currently approved drugs for Alzheimer’s disease – Aricept, Exelon and Razodyne. In 1977, he moved to Albert Einstein College of Medicine in the Bronx. He is currently a Professor in the Departments of Pathology and Neuroscience, and holds the Judith and Burton P. Resnick Chair for Research on Alzheimer’s Disease. Dr. Davies became S cientific Director of the Litwin/Zucker Center for Research on Alzheimer’s Disease at the Feinstein Institute for Medical Research, North Shore/LIJ in 2006. For more than 30 years, Dr. Davies’ research has been focused on biochemistry of Alzheimer’s disease. He has published over 200 research papers, and has been particularly interested in the development of new treatments and diagnostic tests for Alzheimer’s disease.

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