Researchers Slow Alzheimer's, Improve Memory In Mice Using Novel Drug
May 14, 2013

Researchers Slow Alzheimer’s, Improve Memory In Mice Using Novel Drug

Brett Smith for - Your Universe Online

Many Alzheimer´s disease researchers are focused on stopping the buildup of amyloid plaques, dense protein deposits that are a telltale sign of the debilitating disease. However, a group of scientists from the Salk Institute for Biological Studies decision to think outside the box and pursue a different treatment strategy has paid off.

According to their report in the journal Alzheimer´s Research and Therapy, the Salk team has developed a novel drug candidate currently referred to as J147.

"J147 is an exciting new compound because it really has strong potential to be an Alzheimer's disease therapeutic by slowing disease progression and reversing memory deficits following short-term treatment," lead author Marguerite Prior, a researcher at Salk's Cellular Neurobiology Laboratory, said in a statement.

In their report, the team said because testing for amyloid plaques is an effective way to predict risk of contracting the disease, treating Alzheimer´s has focused more on preventing the disease than modifying it.

"Alzheimer's disease research has traditionally focused on a single target, the amyloid pathway," said David Schubert, a professor in the Salk´s Cellular Neurobiology Laboratory, "but unfortunately drugs that have been developed through this pathway have not been successful in clinical trials.

“Our approach is based on the pathologies associated with old age-the greatest risk factor for Alzheimer's and other neurodegenerative diseases-rather than only the specificities of the disease,” Schubert said.

To test the efficiency of the newly developed drug, Schubert and his colleagues, using a preclinical Alzheimer's model, administered it to 20-month-old genetically engineered mice at an advanced stage of Alzheimer's. After a three-month treatment period, the drug reversed severe memory loss, lowered soluble levels of amyloid and raised neurotrophic factors essential for memory.

The scientists also tested J147 directly against the widely-prescribed Alzheimer´s treatment Aricept, and found it performed the same or better in several cognitive tests.

Schubert cited the novel process, which focused more of the symptoms of aging, as one of the main drivers of the discovery.

"In addition to yielding an exceptionally promising therapeutic, both the strategy of using mice with existing disease and the drug discovery process based upon aging are what make the study interesting and exciting," he said, "because it more closely resembles what happens in humans, who have advanced pathology when diagnosis occurs and treatment begins."

Schubert added that their "approach to screening drugs is very different from that currently used by pharmaceutical companies. AD is a complex disease associated with old age, and our goal is to make drugs like J147 that reduce the multiple toxicities associated with the disease, not just one. We believe that J147 is the best AD drug candidate in the pipeline and will be effective if we can get it into the clinic".

In their report, the Salk researchers said several biomarkers associated with Alzheimer's pathology are affected by the novel drug treatment — including an increased brain-derived neurotrophic factor (BDNF), a protein that protects neurons from toxins, assists in neuron growth and is involved in memory creation.

The team added that J147´s general ability to protect nerve cells could make it useful in the treatment of other neurological disorders, such as Parkinson's disease, stroke and amyotrophic lateral sclerosis (ALS), despite the fact their study did not explicitly look at the drug's effectiveness in treating those diseases.