Scientists at the Salk Institute report they have developed a new drug that holds potential for halting the mental decline associated with Alzheimer’s disease. In a study, the drug, known as JI47, improved memory and prevented brain damage in mice.
The study is published in the journal PLoS One.
“J147 enhances memory in both normal and Alzheimer’s mice and also protects the brain from the loss of synaptic connections,” said David Schubert, Ph.D., the head of Salk’s Cellular Neurobiology Laboratory. “No drugs on the market for Alzheimer’s have both of these properties.”
Although it is yet unknown whether the compound will prove safe and effective in humans, the Salk researchers’ say their results suggest the drug is promising for treatment of people with Alzheimer’s.
As many as 5.4 million Americans suffer from Alzheimer’s, according to the National Institutes of Health. More than 16 million will have the disease by 2050, according to Alzheimer’s Association estimates, resulting in medical costs of over $1 trillion per year.
The disease is devastating as individuals experience a steady, irreversible decline in brain function. Memory loss advances until a person is unable to perform simple tasks such as eating and talking. Ultimately, the disease is fatal.
Experts say Alzheimer’s is linked to aging and typically appears after age 60, although a small percentage of families carry a genetic risk for earlier onset. Among the top 10 causes of death, Alzheimer’s is the only one without a way to prevent, cure or slow disease progression.
In the current trial, Schubert and his colleagues developed an innovative strategy of using living neurons grown in laboratory dishes to test whether or not new synthetic compounds were effective at protecting the brain cells against several pathologies associated with brain aging.
Based on the test results from each chemical iteration of the lead compound, which was originally developed for treatment of stroke and traumatic brain injury, they were able to alter its chemical structure to make a much more potent Alzheimer’s drug.
“Alzheimer’s is a complex disease, but most drug development in the pharmaceutical world has focused on a single aspect of the disease–the amyloid pathway,” said Marguerite Prior, Ph.D., a research associate in Schubert’s lab, who led the project along with Qi Chen, Ph.D., a former Salk postdoctoral researcher.
“In contrast, by testing these compounds in living cell cultures, we can determine what they do against a range of age-related problems and select the best candidate that addresses multiple aspects of the disease, not just one.”
The Salk researchers tested J147 as an oral medication in mice and discovered it prevented cognitive decline in animals with Alzheimer’s and that mice and rats treated with the drug produced more of a protein called brain-derived neurotrophic factor (BDNF) — a molecule that protects neurons from toxic insults, helps new neurons grow and connect with other brain cells, and is involved in memory formation.
Because of the broad ability of J147 to protect nerve cells, the researchers believe that it may also be effective for treating other neurological disorders, such as Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis (ALS), as well as stroke.