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Early Results Promising for New Alzheimer Drug
As many as 5.4 million Americans suffer from Alzheimer’s disease. Alzheimer’s disease is expected to afflict over 16 million worldwide by 2050. Recently, however, a new synthetic drug has been developed that may curb that number.
The compound, known as J147, has been shown to halt the progressive brain damage associated with Alzheimer’s in laboratory animals. It also improves cognitive function in animal models of Alzheimer’s disease.
The novel synthetic drug was developed by investigators at the Salk Institute of Cellular Neurobiology in San Diego, Calif. A team of several different labs were involved in the development of the new chemical, followed by biological validation and testing in animal models.
The Salk scientists took a radical new approach different from most pharmaceutical companies that are developing Alzheimer’s disease medications. Many scientists have targeted the biological pathways involved in the formation or clearance of beta-amyloid plaques, a hallmark symptom of the disease. The Salk group, however, focused on chemicals that protected neurons growing in culture dishes from a variety of toxic insults, such as oxygen deprivation.
“Most drug development in the pharmaceutical world has focused on a single aspect of the disease, the amyloid pathway,” said Marguerite Prior, research associate at Salk Cellular Neurobiology Laboratory and lead researcher of the project. “By testing these compounds in living cell cultures, we can determine what they do against a range of age-related problems.”
The investigators were able to elucidate a lead compound and further modify its chemical structure until it protected the brain cells against a variety of age-related problems. Once it demonstrated effectiveness, J147 was tested in lab mice that were genetically engineered to develop Alzheimer’s disease. In collaboration with a lab at the Scripps Institute also in San Diego, the researchers ran the mice through several behavioral mazes that assessed their abilities to learn and store new memories.
While scientists are still unsure about the exact mechanism by which J147 works, they do know it stimulates the production and secretion of a chemical called brain-derived neurotrophic factor (BDNF). BDNF normally protects brain cells against toxicity and, along with other growth factors, has been shown to improve memory in mouse models of Alzheimer’s disease.
J147 represents the first drug that shows promise in both improving memory in the short-term and halting disease progression in the long-term. Currently, the only drugs approved for treatment of Alzheimer’s disease, such as Aricept, Exelon and Memantine, increase memory performance but do nothing to alter the course of the disease.
The next step for the investigators is to see whether the J147 compound works the same way in humans. The drug will be tested in a large multi-center clinical trial to see whether it meets its endpoints in humans. The Salk investigators believe that J147 might be effective for treating other neurodegenerative disorders as well, such as Parkinson’s disease and amyotropic lateral sclerosis (ALS)
The study was published online in the journal PloS One.
January 28, 2012