Novel drug development at Auburn could combat Alzheimer’s disease progression

A researcher in the Auburn University Harrison School of Pharmacy has developed a novel drug for helping to fight the progression of Alzheimer’s disease.

Raj Amin, associate professor in the Department of Drug Discovery and Development, said current drugs that activate the class of nuclear receptors, known as PPAR-gamma or peroxisome proliferator-activated receptor gamma, have traditionally been used for improving insulin sensitivity in diabetic patients. The mechanism for its antidiabetic properties involves improving energy regulation. However, in the brain, activation of PPAR-gamma remains relatively unknown, especially in the case of Alzheimer’s disease. Furthermore, many of these therapies have been designed to lack the ability to cross the blood brain barrier and thus they lack positive effects on the brain.

Unfortunately, he said many of the current PPAR-gamma therapies have been observed to be associated with adverse effects upon human health, including heart failure and bladder cancer.

“Our new therapy, AU9, is a nontraditional selective PPAR-gamma agonist that has been developed computationally to avoid these deleterious effects on human health,” Amin said. “It also displays the ability to cross the blood brain barrier, thus having neuroprotective positive effects in the brain.”

The neuroprotective component of AU9 has been observed in animal models of Alzheimer’s brains to induce specific growth factors called neurotropins that act like neurohormones. These neurotropins help strengthen neurons, as well as form connections with other neurons to allow for establishing memories.

In addition, AU9 also reduces neuroinflammation, and thus it protects the neuron from the neurodegenerative process associated with Alzheimer’s disease.

The team’s research is supported by a $449,999 grant from the National Institutes of Health’s Small Business Innovation Research program. Amin said they are working towards FDA approval to help people with Alzheimer’s disease.

“We want to understand how selective stimulation of PPAR-gamma in the brain offers neuroprotection against memory impairment and neurodegeneration associated with Alzheimer’s disease, as well as diabetes,” said Amin.

Amin is leading the study with Professors Rusty Arnold and Vishnu Suppiramaniam in pharmacy’s Department of Drug Discovery and Development and Satyanarayana Pondugula in the Department of Anatomy, Physiology and Pharmacology in Auburn’s College of Veterinary Medicine and the resources available at the Center for Neuroscience Initiative (CNSI) at Auburn.

In phase one of the two-year grant, Amin will also develop a biotechnology company, Metabolic Therapeutics, at Auburn University, which has several other potential therapeutics being investigated for diseases associated with energy dysregulation, including Alzheimer’s, diabetes and liver disease, specifically nonalcoholic steatotic hepatitis, or NASH.

“We develop our tools computationally and further develop them through cellular and animal models for future potential therapeutics for improving health in the citizens of Alabama,” Amin said.

Phase two will involve a commercialization plan.