~ 121711 Salk Researchers Discover Potential Alzheimer's Drug

~ 121711 Salk Researchers Discover Potential Alzheimer's Drug
Bradley J. Fikes
North County Times, Escondido, Calif.

Dec. 14--LA JOLLA -- A scientific team at the Salk Institute may have found a way to help defuse the demographic, emotional and economic time bomb known as Alzheimer's disease.

The scientists say they've developed a drug that, in a mouse model of Alzheimer's, provides strong protection against the memory loss and dementia associated with Alzheimer's. The drug, called J147, also appears to be safe for animals, and presumably humans, so it could be ready for humans in a couple of years.

The drug not only prevents memory loss, but reduces the brain cell degeneration associated with Alzheimer's. No drug on the market can do both, said Marguerite Prior, a research associate in the lab of Dave R. Schubert, head of Salk's Cellular Neurobiology Laboratory. Prior led the research along with Qi Chen, a former Salk researcher, under Schubert's guidance.

The study tested Alzheimer's model mice and normal mice for their ability to perform tasks such as navigating mazes and remembering the correct path, with and without taking J147 in their food. The study was published Wednesday in PLoS ONE, a peer-reviewed online journal with headquarters in San Francisco and Cambridge, England.

The drug actually improves learning in the Alzheimer's model mice, the paper stated, suggesting that it corrects learning impairment. And the drug also improves learning in normal mice. In general, the paper said, J147 appears to have a broadly protective effective on brain and nerve cells.

The drug can be ready for testing in people soon after a company takes on the project and is willing to commit about $1 million to qualify J147 to begin clinical testing, Schubert said. Since Schubert's lab is dedicated to basic research, the scientists are not qualified to do clinical work by themselves.

So J147 is poised at the tricky hand-off stage from basic research, largely conducted as a nonprofit venture by academic labs like Salk, to clinical development, usually done by for-profit companies. These companies are less concerned with the science than whether the drug can make them a profit big enough to justify their investment.

That means those concerned will have to wait an undetermined amount of time, perhaps two or more years, before J147 gets tested in people -- if it reaches that stage.

For those stressed with caring for someone with Alzheimer's, or who think they may have the disease, the Alzheimer's Association provides information and help. Visit www.alz.org or call the 24/7 helpline at 800-272-3900. For information about Alzheimer's treatments now being tested in people, visit www.clinicaltrials.gov.

Options few

Unlike almost any other major fatal disease, Alzheimer's lacks effective treatment, according to the Alzheimer's Association. Between 2000 and 2008, deaths from HIV fell 29 percent, deaths from stroke by 20 percent and deaths from heart disease by 13 percent. Deaths from Alzheimer's skyrocketed 66 percent.

Alzheimer's is the sixth-leading cause of death in the United States, the association says. Approved drugs can temporarily slow the disease's progression and delay memory loss to a modest extent. But in all cases, the disease progresses in a characteristic pattern from mild symptoms such as an increasingly faulty memory, increased difficulty in performing tasks, impaired arithmetical ability, becoming confused about what day it is or where a person is. At the end, patients lose their ability to converse and to control their movements.

While not all age-related dementia is caused by Alzheimer's, it is the most common form. And about 4 percent of Alzheimer's patients develop the disease in their 40s and 50s, called early-onset Alzheimer's.

Without some major breakthroughs, an aging population of baby boomers seems guaranteed to send the numbers of Alzheimer's deaths soaring, as well as increasing the burdens of partners and relatives who look after them.

As of 2011, 5.4 million Americans have Alzheimer's. The cost of their care has reached $183 billion, according to the Alzheimer's Association. By 2050, as many as 16 million Americans could have the disease, at an unknown but certainly far higher cost than today.

Schubert said his lab approached Alzheimer's in part by avoiding what wasn't working in research, namely a hypothesis that protein plaques of a type called beta-amyloid are the key to Alzheimer's. These beta-amyloid plaques, according to the hypothesis, accumulate in the brain cells of Alzheimer's patients, progressively impairing their function.

Trouble is, big pharmaceutical companies have already sunk a lot of money into drugs developed on the amyloid theory, and they've all failed, Schubert said.

New thinking

That failure suggested trying a different approach with Alzheimer's. So the researchers looked for drugs that reduced signs of the disease in mice, and that also reduced the age-related cellular damage associated with the disease. They studied cultures of mouse brain cells that produced signs of damage to the central nervous system. Only drug candidates that blocked all the various signs of damage were then tested in whole mice.

One of these drug candidates was derived from curcumin, a chemical found in the spice turmeric. Curcumin has been studied for years because of evidence it provides some protective effect against Alzheimer's, as well as potentially some cancers and strokes. The original molecule has been altered to increase effectiveness, so it is now quite different from the natural compound, Prior said.

The researchers evaluated safety in years of study on mice bred to develop a genetic condition similar to that of inherited Alzheimer's in people, said Prior, the research associate. The mice given the drug scored dramatically better in various tests of memory and thinking than the Alzheimer's mice that were not given the drug.

"We feed the drug to the mice in their food," Prior said. "We've done some long-term studies and we don't see any side effects. We have also sent the drug to outside companies to do some toxicity (testing), and they see the same results. They see no toxicity problem. We expect it to be safe in humans, if it ever gets that far, which we hope it will."

Schubert said the drug is ready now for what's called an IND, or Investigational New Drug, application to the U.S. Food and Drug Administration. With an approved IND, a drug company can take J147 out of the lab and get it into patients.

A San Diego-area company is interested in licensing the drug, and discussions are under way, Schubert said. Since there is as yet no agreement, he declined to disclose the company's name.

More on this discovery.

Call staff writer Bradley J. Fikes at 760-739-6641.


(c)2011 the North County Times (Escondido, Calif.)

Visit the North County Times (Escondido, Calif.) at www.nctimes.com

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