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New Treatments for Alzheimer’s Disease From Rockefeller Institute

November 30, 2004

MORGANTOWN, W.Va., Nov. 30 /PRNewswire/ — Two new drug treatments for Alzheimer’s disease, developed at the Blanchette Rockefeller Neurosciences Institute (BRNI), have won patent protection and could be available for testing by volunteer patients in the next several months. Both treatments act on molecular targets discovered by BRNI scientists within memory signaling pathways of the brain.

On Nov. 23, the U.S. Patent and Trademark Office approved a combination therapy developed by Daniel Alkon, M.D., scientific director of BRNI and Miao- Kun Sun, Ph.D., also of the BRNI research faculty. In animal tests, they discovered that a combination of two substances already in the human diet, methylxanthine (in tea), and phenylalanine, a carbonic anhydrase activator (in aspartame), increased the ability of research subjects to focus attention. “Carbonic anhydrase plays a crucial role in the formation of memories,” Dr. Alkon said. “This compound could help focus attention, allowing us to fully concentrate on creating a memory.” One of the earliest symptoms of Alzheimer’s disease is the loss of short-term memory. By activating the carbonic anhydrase already present in the body, the drug could enhance the attention of patients.

Alkon and Sun first showed that carbonic anhydrase controls electrical brain activity in rats called theta rhythms (also seen in humans). These brain waves are seen when the rats are paying attention. They then identified drugs that enhance attention by activating carbonic anhydrase. The carbonic anhydrase activator, phenylalanine, is an ingredient in the commonly used artificial sweetner aspartame. Methylxanthines include a number of compounds with stimulant effects, such as caffeine and theophylline, ingredients of coffee and tea. Theophylline, previously used to treat asthma patients, increases the attention-enhancing effects of carbonic anhydrase activation.

Today (Nov. 30), the USTPO approved another BRNI patent. The Institute now holds patent protection for the use of bryostatin — originally developed as a cancer drug — to treat Alzheimer’s disease. Bryostatin works by activating an enzyme called protein kinase C, which enhances the activity of another key protein called alpha secretase. This protein plays a role in processing amyloid precursor protein, a central element in Alzheimer’s disease progression. Bryostatin has been shown to be effective in enhancing recent memory as well as in reducing the levels of soluble beta amyloid in mice with the Alzheimer’s gene and, most likely, the protein deposits of beta amyloid called plaques.

In the mice, bryostatin worked to treat both the symptoms, including memory loss, of Alzheimer’s disease and the underlying cause of the disease. It is believed that bryostatin will have the same effect in humans. “The medications currently used to treat Alzheimer’s disease only treat the symptoms, and with limited benefit,” said Alkon. “They do not treat the underlying medical condition that is causing the symptoms. These medications treat both the symptoms and the cause of the disease by affecting the formation of memories themselves.”

Both the carbonic anhydrase activator and bryostatin have already been approved by the Food and Drug Administration for other uses in humans. Because both of these drugs are approved for human use, the approval process for testing them as Alzheimer’s treatments should be much shorter. Clinical trials with both drugs in Alzheimer’s patients could begin as soon as six to eight months.

“The patent positions give BRNI a government-protected right to use these methods to treat Alzheimer’s disease and other cognitive problems such as attention-deficit disorder,” Alkon said. It is estimated that 4.5 million Americans have Alzheimer’s disease, which has no cure and is always fatal. In addition, more than 16 million Americans are expected to have Alzheimer’s by 2050 as the baby boom generation ages. Memory loss is the first symptom that is noticed when recent memories are affected.

BRNI is the only non-profit institute with a dedicated study of both human memory and diseases of memory. Its primary mission is to accelerate neurological discoveries from the lab, including diagnostic tools and treatments, directly to patients who are suffering from neurological diseases such as Alzheimer’s. It is operated in collaboration with West Virginia University in Morgantown and Johns Hopkins University in Baltimore. Sen. Jay Rockefeller of West Virginia founded the institute in memory of his mother, who died of Alzheimer’s disease.

Patent references:

Carbonic anhydrase activator: U.S. Patent 6,821,979, Alkon, et al. Nov. 23, 2004, “Synergistic enhancement of cognitive ability.”

Bryostatin: U.S. Patent 6,825,229, Etcheberrigaray, et al. Nov. 30, 2004, “Methods for Alzheimer’s disease treatment and cognitive enhancement.”

West Virginia University

CONTACT: Liz Cousins, HSC News Service, of West Virginia University,+1-304-293-7087, or cousinse@rcbhsc.wvu.edu




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