issue Summer 2021

The Journey Toward Stronger Alzheimer's Treatments

By Margaret Smith
Drs. Stutzmann (left) and Buolamwini
Photo by Michael R. Schmidt

For over a decade, the Stutzmann lab and collaborators such as John Buolamwini, PhD, have been dedicated to identifying novel therapeutics to combat Alzheimer’s disease. What sets the recent project apart from similar efforts is the use of in silico drug design and screening by the Buolamwini lab, and incorporating computer-based validation tools used by drug companies.

“Together, we’re working to develop novel molecules that will reduce the amount of toxic or pathological signaling within neurons and then to develop these CNS-targeted drugs,” said Grace E. Stutzmann, PhD, director of the Center for Neurodegenerative Diseases and Therapeutics. “The in silico design refers more to the computational, deductive means to draw or develop new compounds or molecular structures — and not the wet lab procedures of mixing and stirring and incubating, but rather using computer-generated methods.”

The team behind the project, in conjunction with Dr. Stutzmann’s startup company NeuroLucent, includes lab members and teams from across campus — such as Dr. Buolamwini, who is professor and chair of the Department of Pharmaceutical Sciences, College of Pharmacy. Team members also include RFU stakeholders such as Robert Marr, PhD, also in the Center for Neurodegenerative Diseases and Therapeutics.

Dr. Stutzmann described Dr. Buolamwini’s role as “central to our project. As a medicinal chemist, he and his lab are designing, creating and generating the actual compounds that we are testing, as well as overseeing any outsourced chemistry screens and assays.” Dr. Buolamwini provides oversight of all the drug-based chemistry data that is generated so he can work to optimize the composition of the compounds.

The latest addition to the team is a company that specializes in mathematical modeling through artificial intelligence to build compounds. The objective is to compile data from the project and use the predictive modeling of AI to foresee which compounds could prove to be the most beneficial.

For me, it is an incredible journey. I would love nothing more than to speed it up for the overall good of humankind and to reduce all that suffering that comes with this disease.

Dr. Stutzmann has watched the integration of technology and medicine unfold over the last decade, something she calls an “enlightening experience.” While the end goal is providing safe and effective drugs for Alzheimer’s patients, getting there isn’t exactly linear, nor is it simple.

Funding and comparing and contrasting the most effective screening methods are just some of the barriers Dr. Stutzmann described when it comes to getting a drug out of the lab and into the pharmacy. She suggests there still might be another decade of research between now and then. In the meantime, she added, the project will focus on short-term goals, such as creating “combinations and permutations of existing compounds to identify the best lead candidates, and then determine which tools to use to identify the most promising ones. ...We should, by no means, have to pick (just) one.”

The motivation of this project, for Dr. Stutzmann, is double-sided. While the project’s main goal is undoubtedly finding the most effective way to treat Alzheimer’s, it simultaneously is bringing AI-driven medicine into the mainstream and making room for alternative research methods.

Additionally, personal to Dr. Stutzmann, actualizing this mode of research — which at one time was what she called just a “percolating and developing” concept — is monumental.

“Even approaching something that could potentially have a clinical benefit is overwhelming in satisfaction. For me, it is an incredible journey. I would love nothing more than to speed it up for the overall good of humankind and to reduce all that suffering that comes with this disease,” Dr. Stutzmann said. “But for me ... it will just have to take as long as it takes. We’re not going to leave the project.”