Dr. Hussein Yassine’s lab in the Keck School of Medicine of USC received an $8 million grant from the National Institutes of Health in September. The funding will be distributed over the next five years of their project aimed at developing a groundbreaking drug for Alzheimer’s disease. 

The team — led by Yassine, a professor of neurology at Keck — brings together experts across pharmacology, radiology and computational biology to explore a new approach to neurodegeneration.

“The goal is to develop a drug that targets brain inflammation to see whether lowering inflammation can decrease the severity of neurodegenerative diseases like Alzheimer’s,” Yassine said.

The researchers believe that inflammation, triggered by the enzyme cPLA2, plays a key role in initiating Alzheimer’s disease; their goal is to block this enzyme. Using advanced computational tools, they searched for molecules — also known in this case as compounds — that can effectively inhibit cPLA2. The team identified a few promising compounds that will be tested before they settle on one to be turned into a drug. 

Yassine said the project was driven by collaboration with students, postdoctoral scholars and faculty to test their hypothesis that inflammation of the brain causes Alzheimer’s.

“This was really a team effort … over 30 people worked on this project,” Yassine said. “It took multiple cycles of applying, refining and getting stronger data before we got here.”

Dr. Vsevolod Katritch, a professor of quantitative and computational biology at the Dornsife College of Letters, Arts and Sciences, led the computational modeling efforts.

“We used physics-based and AI tools that allow us to screen libraries now, [searching through] trillions of compounds,” Katritch said. “We found compounds that bind to the enzyme and block its action.”

The team’s promising findings won them the $8 million grant. Now, Dr. Stan Louie of the School of Pharmacy can start working on translating the team’s discoveries into a viable medicine — refining its formulation, testing its safety and determining how it behaves in the body.

Developing a drug for Alzheimer’s poses several challenges. The brain’s protective barrier makes it difficult for treatments to reach their target, and even promising compounds can behave unpredictably once they enter living tissue. The team must also balance safety with effectiveness, finding a dose that reduces inflammation without disrupting normal brain function.

Dr. Kai Chen, a professor of research radiology and radiation oncology at Keck, leads the project’s imaging and radiology efforts. Chen uses PET imaging to track how the different compounds interact with the brain and reduce inflammation in real time.

“Imaging plays an indispensable role in drug discovery,” Chen said. “Without imaging, we are kind of going in the dark to see which compound we should choose and whether it’s responding to the treatment in the real world.”

For those involved, the effort represents more than just another research milestone. It’s a university-wide collaboration that unites experts in several fields, reflecting the potential of what can be done when separate disciplines come together toward a shared goal. 

Beyond Keck’s laboratories, USC students are also working on Alzheimer’s in their own way. Members of National Alzheimer’s Buddies at USC spend several afternoons each week connecting with residents at a local senior living facility, offering companionship and comfort to those living with the disease. 

For Owen Chen, a club member and a sophomore majoring in computational neuroscience, the club offered him an intimate perspective on how Alzheimer’s impacts people.

“One patient that I interact with frequently, we often talk about her job,” Chen said. “She only talks about it, and it’s really rough to see because we’ve had some really great conversations, but sometimes it just devolves into her talking incoherently about her job. And I know she has a lot more to share about herself.”

Baishali Chaudhuri, the treasurer of National Alzheimer’s Buddies at USC and a senior majoring in biochemistry, said the project represents a new sense of hope.

“Alzheimer’s is truly such a dehumanizing disease — it really does take small bits of you as it progresses,” Chaudhuri said. “Having a drug that [could] allow someone to keep parts of who they are for longer [would be] truly amazing.”