Auburn University pharmacy team developing new Alzheimer’s therapy

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The Harrison College of Pharmacy’s Raj Amin has received $1.1 million in support from the National Institutes of Health for the development of a compound that could help certain individuals who may be more susceptible to Alzheimer’s disease at an earlier age.

The project, titled “Evaluation of a specific LXR/PPAR agonist for treatment of Alzheimer’s disease,” is funded by the National Institute of Neurological Disorders and Stroke—Innovation Grants to Nurture Initial Translational Efforts program, or IGNITE.

The Amin lab is developing a compound referred to as AU403IS, which may help individuals with the APOe4 allele, a genetic variant that may make certain people more susceptible to Alzheimer’s disease at an earlier age.

“I am very excited about the abilities the NIH gives to us to advance our studies and allow us to proceed with the advancement of our novel drug via the IGNITE program,” said Amin, an associate professor in the college. “Our abilities to design and develop novel therapeutics at Auburn in the Department of Drug Discovery and Development will allow us to advance the field of drug discovery related to fighting Alzheimer’s disease.”

AU403IS, an intellectual property made and designed at Auburn University and the Harrison College of Pharmacy, is a novel drug that activates the nuclear receptor liver-X receptor beta, or LXR beta, and peroxisomal proliferator activating receptor alpha, also referred to as PPAR alpha.

Activating LXR beta may help in regulating APOe4 in the brain. The research this grant supports helps to further understand how AU403IS can have potential therapeutic effect for patients with the APOe4 allele and Alzheimer’s disease.

The compound was designed and synthesized by Ian Steinke, a pharmaceutical sciences graduate student in the medicinal chemistry option, and collaborators, including Robert Arnold and Forrest Smith from the Harrison College of Pharmacy and Satyanarayana Pondugula, professor in the Department of Anatomy, Physiology and Pharmacology at the Auburn College of Veterinary Medicine. Amin and Smith are co-advisors for Steinke in his graduate research.

Steinke, a native of Alpena, Michigan, came to Auburn after completing his degree in chemistry at Ferris State University. He was introduced to Auburn during his undergraduate time as he participated in the synthesizing and development of the AU9 drug, which is now supported by its own phase 2 NIH STTR Research Program grant with Amin.

“Ian is the best graduate student whom I have had the privilege of mentoring at Auburn. We were able to recruit Ian from Michigan, in part because of our unique graduate program that we offer,” said Amin.

Amin points out that graduate students are vital to the innovative work going on at the Harrison College of Pharmacy and across the Auburn campus.

“The Department of Drug Discovery and Development allows students to learn and develop research skills in the areas of medicinal chemistry, pharmaceutics and pharmacology, as well as cross-disciplinary programs,” said Amin. “Ian chose to do a program in medicinal chemistry and pharmacology, allowing him to learn in silico modeling and development of novel targeted therapeutics for Alzheimer’s disease and other metabolic related diseases.”

The in silico design and development of AU403IS means it was designed and developed by computer simulation. The unique properties of the compound help to alter the cholesterol pattern in the brain for patients, resulting in helping reduce pathology and inflammation associated with the progression of the disease.

“Our drug candidate is unique because it has been designed in silico to activate the nuclear receptor LXR and PPAR,” said Amin. “This is a very exciting and promising field with lots of challenges and opportunities to explore, including considerable testing needed for evaluating the safety, efficacy and bioavailability this substance. We hope this compound may help individuals with the APOe4 allele.”

With all the work to get AU403IS to this point in the process, Amin is also thankful for the support and opportunities at Auburn and the Harrison College of Pharmacy to design and develop such a novel drug.

“We are fortunate in the Department of Drug Discovery and Development that personnel and equipment are available for the discovery, design and development of novel drugs for various diseases,” said Amin. “I sincerely appreciate the tremendous support from the department, the college, the dean’s office and Auburn University that allows us to compete at the highest level in the field of drug discovery.”

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Auburn University's Harrison College of Pharmacy is ranked among the top 20 percent of all pharmacy schools in the United States, according to U.S. News & World Report. Fully accredited by the Accreditation Council for Pharmacy Education (ACPE), the School offers doctoral degrees in pharmacy (Pharm.D.) and pharmaceutical sciences (Ph.D.) while also offering a master's in pharmaceutical sciences. For more information about the School, please call 334.844.8348 or visit the Harrison College of Pharmacy website.