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Neuroscientists at the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia will begin a clinical trial testing a new type of drug that attacks amyloid, the protein substance that accumulates in the brains of Alzheimer’s disease patients. The buildup of amyloid and the formation of tangles and plaques in the brain are thought to be major causes of the mind-robbing ravages of Alzheimer’s disease.

Jefferson University and professor of psychiatry and neurology at Jefferson Medical College, and Samuel Gandy III, M.D., Ph.D., director of the Farber Institute for Neurosciences and professor of neurology and biochemistry and molecular pharmacology at Jefferson Medical College, are participating in a multicenter clinical trial to examine the effectiveness of a drug, Alzhemed, in halting the development of amyloid plaques – and the progression of the disease – in individuals with mild to moderate Alzheimer’s.

Currently available medications such as Aricept, Reminyl, Exelon and Namenda treat only disease symptoms, explains Dr. Rovner.

Alzhemed is designed to act differently. “What’s exciting about Alzhemed is that it works directly on the amyloid protein,” says Dr. Rovner.

Alzhemed is being investigated as a “disease-modifying” medication, he notes, with the objective to change the disease. “The hope is that it stabilizes the course of the disease, modifying its progression,” Dr. Rovner says. “It’s aimed at what is thought to be the central problem in the disease – the buildup of protein in the brain that disrupts its message system.”

The drug actually physically combines with amyloid to prevent plaque formation. It also is expected to inhibit the inflammatory response associated with amyloid buildup in Alzheimer’s.

Drs. Rovner and Gandy will lead the Jefferson participation in the trial. The trial is scheduled to last 18 months, and will enroll about 950 Alzheimer's patients with a mild-to-moderate form of the disease. About 50 centers in the United States and 20 in Canada will participate. Jefferson will enroll approximately 15 patients.

Participants are randomized to one of three treatment arms in the trial. One group of patients will receive 100 mg of Alzhemed twice a day. Another group will receive 150 mg of Alzhemed twice a day, while a third group will get a placebo. The trial is double blind, meaning neither the participants nor the doctors know who is receiving treatment. To be eligible, patients need to be on one of the existing Alzheimer’s medications for four months. Potential participants are screened for eligibility using a cognitive skills test.

“What is unique about this trial is its length – 70 weeks,” says Dr. Rovner. “Most drug trials don’t last that long, but because we are investigating

Alzhemeds’ impact on disease course, the extended followup is necessary to examine more precisely whether a disease-modifying effect occurs,” he adds.

There currently is no effective medication to treat Alzheimer's, which affects more than 4.5 million people in the United States alone, a figure expected to triple as the population ages. The disease gradually destroys memory and the ability to think.

Current U.S. Food and Drug Administration-approved drugs called cholinesterase inhibitors don’t work on the amyloid protein, Dr. Rovner explains. They block enzymes that degrade acetylcholine, a neurotransmitter important for memory in the central nervous system. They treat the symptoms, not the underlying disease. Four drugs – Aricept, Exelon, Reminyl and Tacrine – are approved to treat the symptoms of mild-to-moderate Alzheimer’s. A fifth drug, Namenda, which works on a different neurotransmitter, was approved last year for moderate-to-severe cases.

Dr. Gandy, who is also vice chair of the Alzheimer’s Association’s Medical and Scientific Advisory Council, explains that a natural substance in the body called glycosaminoglycan binds to amyloid protein and facilitates amyloid sticking together to form plaques. Alzhemed binds amyloid instead and prevents the glycosaminoglycan from promoting amyloid deposition. It reduces the amount of amyloid in the central nervous system’s cerebrospinal fluid, which bathes the brain and spinal cord. To date, there have been no serious side effects related to Alzhemed reported, although some people have had mild, transient nausea or vomiting.

“Presumably,” Dr. Gandy says, “an Alzheimer’s patient would take the drug for the rest of his or her life.”

The success of failure of the trial will be measured in periodic cognitive skills monitoring before, during and after the 70 weeks. The researchers will also examine brain volume by magnetic resonance imaging before and after the trial.

The trial is funded by Neurochem, Inc., a drug development company headquartered in Laval, Canada.