July 2, 2004 A new drug that appears to improve learning and memory in animals and may reduce the accumulation of destructive plaque that is the hallmark of Alzheimer’s disease is under study at the Medical College of Georgia.
MCG is enrolling Alzheimer’s patients with mild to moderate memory loss in a 12-week study that compares different doses of the drug - still known only by a number - to placebo. The study is being conducted at approximately 40 sites worldwide, including 34 sites in the United States.
“We want to see if this drug will improve cognition or memory in Alzheimer’s disease,” said Dr. Jeffrey L. Rausch, psychiatrist, vice chair of the MCG Department of Psychiatry and Health Behavior and a principal investigator on the study.
The drug, developed by Sanofi-Synthelabo, Inc., in France, has been shown in published studies to improve episodic memory (using an object recognition task) and to reverse learning decline in aging rats, Dr.Rausch said.
Previous clinical trials have suggested the drug is safe in humans; the current study will look at its efficacy and safety.
The drug is among the first to target 5HT4 receptors, one of the numerous receptors that regulates serotonin, a neurotransmitter that enables cells to communicate. Patients with clinical depression often have too little serotonin activity. Many antidepressants work by maximizing the serotonin patients do have.
Although there is no evidence that Alzheimer’s disease directly affects 5HT4 receptors, there is some common ground. 5HT4 activity is associated with an increased excretion of a soluble form of the amyloid precursor protein sAPPá.
However, the insoluble form of this protein deposits in plaques in the brains of Alzheimer’s patients. “Stimulation of the 5HT4 receptors appears to be neuroprotective and memory enhancing in animals,” Dr. Rausch says. Soluble amyloid protein, which can move easily around cells without getting stuck, has antioxidant properties for scavenging free radicals and other potentially destructive trash in the brain.
The new drug under study appears to have a synergistic action with acetylcholinesterase (AChE) inhibitors, which are used to treat symptoms of Alzheimer's disease and which regulate the acetylcholine system, a major neurotransmitter system. A progressive loss of acetylcholine is considered a major culprit in the memory loss that accompanies Alzheimer's; some of the Alzheimer’s drugs already on the market also work to increase acetylcholine, Dr. Rausch said.
This new drug stimulates 5HT4 receptors which are critical to memory and adaptation to the environment. Dr. Rausch noted that Alzheimer’s patients often become irritable and inflexible as their disease progresses, functioning best in a familiar environment and often unable to adjust to a new one. “If you put them in a new environment, their ability to learn and adapt to new things is not there and you may see more dysfunction,” he said.
“We hope this new drug, which is among the first to target this particular serotonin receptor, will indicate a new way of treating this devastating disease,” Dr. Rausch said. “If the study finds the drug successful, perhaps it can one day be used to delay disease progression until a cure for Alzheimer’s can be found.”
For more information about the study, call coordinator Kay Bingham at (706) 721-7835.
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