Using AI to advance brain therapeutics

What if the body had a shuttle service to deliver medication directly to the brain? One research team believes they might have a way to make it a reality.

Peter Davies, MD, PhD, deputy director at the Texas A&M Health Institute of Biosciences and Technology, and his colleagues have been awarded a Dementia and Alzheimer’s Initiative (DARI) seedling grant from Texas A&M Health for their proposal to deliver medication past the blood-brain barrier, a persistent obstacle in neuroscience.

A protective barrier—and a major challenge

The blood-brain barrier is a network of protective mechanisms that blocks unwanted molecules, like drugs or proteins, from entering the brain from the bloodstream, Davies said. While essential for protecting the brain, it also prevents many promising therapeutics from reaching their target.

“What we’re proposing to do is to take advantage of the physiological pathways that the body does use to move specific molecules out of the bloodstream and into the brain,” said Davies, who is also a professor at the Texas A&M Naresh K. Vashisht College of Medicine. “These pathways allow some critical materials and nutrients that are in the bloodstream to be delivered into the brain. Basically, the strategy here is to develop our own synthetic molecules that can move as passengers in that system and move drugs or therapeutics into the brain for both the diagnosis and treatment of brain diseases.”

Davies is working with Wenshe Liu, PhD, Regents Professor and the Harry E. Bovay, Jr. Chair in Chemistry in the Texas A&M College of Arts and Sciences. Together, they hope to target neurodegenerative and neuroinflammatory diseases such as Alzheimer’s disease, Parkinson’s disease and Frontotemporal Dementia (FTD), as well as head injuries that result in post-traumatic encephalopathy.

Turning peptides into “shuttles”

The synthetic molecules the team is creating are a type of peptide—a string of amino acids. They plan on using the synthetic peptides as shuttles from the bloodstream and through the blood-brain barrier to deliver therapeutics into the brain. This is made possible by the peptide’s construction and its ability to interact with target proteins in a very specific way that allows movement from the bloodstream into the brain.

The collaboration between the two researchers stems from the expertise of Liu’s team in designing and developing novel peptides.

The development of peptide shuttles is notable, but the team also has a unique design and development method involving a mix of computational biology, old-fashioned chemistry and artificial intelligence that makes the project even more impressive.

The DARI grant allows for continued support and funding for Vicente Rubio, PhD, a post-doctoral fellow, affiliated with the Department of Translational Medical Sciences and the Center for Translational Cancer Research at the Institute of Biosciences and Technology, who is currently working on these peptides.

“I lead the development of a platform that combines artificial intelligence, computational design and experimental biology to discover peptide shuttles that can cross the blood-brain barrier,” Rubio said. “What’s most exciting is the potential to accelerate the process of finding and optimizing these peptide shuttles. By making the discovery process faster and more efficient than traditional approaches, we’re helping move promising therapies for neurological diseases closer to reality.”

The support, he continued, is essential. Grants like this one provide resources for researchers to gather key data and move closer to a real-world application, he said.

While other researchers have explored similar theories surrounding the blood-brain barrier, this team’s implementation of artificial intelligence sets them apart.

“We use artificial intelligence to design new peptides, test them experimentally, and then use those results to further refine our designs,” Liu said. “We have a healthy feedback loop that not many other teams have that really enhances our ability to push further in drug development.”

Building toward future therapies for brain diseases

While the project is still in early stages, the team’s goal for this grant cycle is to establish foundational data by demonstrating the feasibility of their approach. Success here will lay the groundwork for larger-scale funding and further development, potentially leading to new therapeutics for early intervention in brain diseases.

“I am continually impressed and grateful that Texas A&M is willing to invest in launching these early-stage initiatives in order to have the research progress to a level where it can be expanded and can compete successfully for extramural funding,” Davies said. “It’s admirable that the institution has made the strategic decision to support early phase research that can be important, ultimately, in having the university take a leading role in this field of research.”

By Lasha Markham, Texas A&M Health