Ongoing Clinical Trial for Anti-Cancer Drug Found to Restore Brain Function in Alzheimer’s Disease Rodent Model

Researchers at Yale University School of Medicine in New Haven recently published in the journal Annals of Neurology the finding that a specific experimental anti-cancer drug can be used as an effective therapy for Alzheimer’s disease. The study is entitled “Fyn inhibition rescues established memory and synapse loss in Alzheimer mice” and was funded by the National Institutes of Health as part of an initiative to repurpose experimental drugs.

Alzheimer’s disease is the most common form of dementia and corresponds to a neurodegenerative disorder where individuals initially experience memory loss and confusion that gradually leads to behavior and personality changes, a decline in cognitive abilities, and ultimately the severe loss of mental function. The disease is characterized by the brain formation of amyloid plaques (containing beta-amyloid proteins), and the loss of neurons that are responsible for memory and learning. Alzheimer’s is estimated to be the sixth-leading cause of death in the United States with 5.3 million Americans suffering from the disease. There is no cure for Alzheimer’s disease and the current available therapies ease the symptoms but do not block disease progression.

Researchers have now discovered that the drug saracatinib (AZD0530, AstraZeneca), originally developed as an anti-cancer drug, has a therapeutic effect in Alzheimer’s mouse models. Saracatinib targets a protein named Fyn kinase, which was previously shown to have an important role in the brain cell damage induced by amyloid plaques. The team found that saracatinib treatment for four weeks restored memory loss and completely reversed spatial cognitive impairment in Alzheimer’s mouse models. The drug was well tolerated by the animals.

“The investigational drug already had been developed, optimized and studied in animals as well as tested for safety in humans, so our ability to obtain this asset through NCATS [National Center for Advancing Translational Sciences] and AstraZeneca gave us an incredible shortcut in the drug development process,” explained the study’s senior author Dr. Stephen Strittmatter in a news release.

As saracatinib had already been tested for safety as an anti-cancer drug, the research team could surpass this part in the drug development process, which can take at least a decade. Within 18 months, researchers conducted the required preclinical and clinical safety studies and initiated human clinical trials to assess the safety and efficacy of the drug in Alzheimer’s disease.

“This work demonstrates what can happen when NIH, the biopharmaceutical industry and academia innovate and collaborate to share resources and knowledge,” said NCATS Director Dr. Christopher P. Austin. “The speed with which this compound moved to human trials validates our New Therapeutic Uses program model and serves NCATS’ mission to deliver more treatments to more patients more quickly.”

“This program enabled us to pair AstraZeneca’s data on this compound with the Strittmatter group’s specialized Alzheimer’s disease knowledge to uncover a potential new therapeutic use for saracatinib. It’s a great example of how scientists from industry and academia can synergistically work together to push the boundaries of medical science,” said Dr. Craig D. Wegner, Head of Boston Emerging Innovations Unit, Scientific Partnering & Alliances within AstraZeneca’s Innovative Medicines and Early Development.

The team has already completed a successful Phase 1b safety human clinical trial for Alzheimer’s disease (NCT01864655) and is currently enrolling participants for a Phase 2a trial (NCT02167256) to evaluate the safety, tolerability and effectiveness of saracatinib.

Individuals interested in participating in this clinical trial can find more information here.