Alzheimer's drug treatments flourish – then flounder

December 5, 10:56 AMScience News ExaminerMeg Marquardt

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Agustine D., the first AD patient described by Alzheimer in 1906.

As we leave Alzheimer's Awareness Month, I take an in-depth look at the history and exciting future of AD treatment. Part I of this piece, a historical overview of AD, can be found here.

Part II: Drug Treatments Flourish – then Flounder

In a search for information on the field of Alzheimer disease (AD) treatment, I was happily surprised to find an expert right here in Omaha. Dr. William Burke, Vice Chair of the Department of Psychiatry at the University of Nebraska Medical Center (UNMC), showed me to his office, a comfortably large room tucked away in the back corner of the hallway.  We sat a small circular table, and I flipped open the notebook, offering my first question, one about his expertise.  A cursory search into his work at UNMC had revealed that he specialized in "psychopharmacology," a field, he explained, that dealt with the drug treatment of psychiatric diseases from schizophrenia to depression. His true specialty was in geriatric psychiatry, dealing with patients over the age of 65 who face, most prominently, depression and dementia.  His work with drugs was twofold: testing new up-and-coming drugs and finding new uses for existing drugs.

We started the discussion with existing pharmaceutical treatments for AD.  There are currently four drugs approved by the FDA: Aricept, Razadyne, Exelon, and Namenda.  The first three are known as cholinesterase inhibitors.  These drugs help improve the brain's ability to both process and increase the amount of acetylcholine, a chemical messenger that is thought to be important in memory functions.  Namenda also works to increase the levels of a chemical messenger—this time glutamate, also known to aid in memory function—in the brain.  Dr. Burke estimates that they are effective for approximately 20-30% of patients and have very few side effects, almost all of which are mild.  "[The drugs] are modestly effective," he states, "and worthwhile as there aren't any other options."

The low levels of effectiveness can be attributed to the fact that they are "symptomatic" drugs: they treat the symptoms of the illness, not the cause of it.  Memory impairment is a hallmark of AD, but it is in no way the underlying reason behind the disease itself.  It is the plaques and tangles that form on the brain during AD that pose the real threat, but at the moment there is no pharmaceutical treatment available to deal with these physical symptoms.

The rush to find a treatment for AD has been newly revitalized in recent years, especially in America.  As the Baby Boomer generation creeps ever closer to the average onset age of 60, money for research from the National Institute of Health (NIH) continues to grow rapidly.  In 2007, over $600 million was allotted to AD studies, making it the 4th highest funded area of research, just behind HIV/AIDS, Cardiovascular diseases, and diabetes.  But is the money enough?  There are those who question the large sums of money that are continuously being poured into AD research even though the only results have been, in a word, disappointing.

With a large generation of people moving towards the age of Alzheimer’s, the level of frustration surrounding the failed drug Flurizan was unsurprisingly large.  Flurizan was the first drug that specifically targeted the Aβ plaques in the brain and had spectacular results in the clearance of the plaques in laboratory experiments on mouse models of AD.  There was a great hope when Flurizan entered into the FDA’s rigorous human clinical trials.  FDA trials are composed of four phases: 1. A small group of normal, healthy individual to test for side effects, 2. A small group of patients suffering from the specific disease, again to test for side effects and general effectiveness of the drug, 3. A larger group of patients (usually 100 or more) to test the true effectiveness of the drug, usually consisting of an experimental group and a control group taking a placebo drug, and 4. FDA surveillance of the drug after it has been released to the general population.  Flurizan proceeded to Phase III with little problem and encouraging data, but as the results of Phase III returned in early 2008, the truth of the matter was plain: Flurizan simply didn’t work.  There was no significant difference in patients taking the drug and those taking placebos.  Peter Meldrum, President and CEO of Myriad Genetics, the company behind Flurizan, stated quiet simply that the company would halt the development of the drug. “We are disappointed that Flurizan failed to achieve significance in this study,”  he stated, capturing the feelings of all those who had so hoped for the drug to work. 
    
Check back Monday for Part III: A Light in the Dark