With federal funding, University of Michigan researchers test promising way to achieve elusive blood-brain barrier crossing to target immune cells responsible for disease
RESEARCH TO WATCH
WHAT'S THE STUDY: A National Institutes of Health grant will fund research at the University of Michigan that tests the theory that an IV-delivered antibody treatment can cross the brain's protective barrier, one of the biggest hurdles in treating Alzheimer's disease.
The engineered antibody shuttles are noninvasive, and target genes and immune cells involved in the disease. Specifically, the investigators, led by researchers from the College of Pharmacy, College of Engineering and including other specialties, are developing a new way to control gene activity in microglia, the immune cells that help maintain the brain but can also contribute to inflammation and neurodegeneration. The researchers seek to overcome the challenge of getting medicines directly to the microglia throughout the brain.
WHY IT MATTERS: More than 7 million Americans (and an estimated 33-38 million people worldwide) currently live with Alzheimer's disease. Other forms of dementia and neurological disease affect millions more. These numbers are growing and are expected to increase. Finding effective treatments and medications that reach the cells in the brain, however, is extremely challenging. Such an achievement could save lives and improve quality of life for patients, their families and caregivers who are affected by Alzheimer's and other dementias. If the approach proves out in this research project, it could lead to clinical trials.
HOW MUCH AND FOR HOW LONG: The $3.1 million project R01 grant runs for five years through November 2030.
WHO IS INVOLVED:
Peter Tessier, the Albert M. Mattocks Professor of Pharmaceutical Sciences at the College of Pharmacy and professor of chemical engineering at the College of Engineering. His lab engineers antibodies capable of transporting drugs from the bloodstream to the brain. His focus is developing best-in-class therapeutic antibodies and next-generation technologies that can be applied to multiple key biomedical challenges-from antibodies that activate T cells for treating cancer to neutralizing antibodies for treating COVID-19 and other infectious diseases.
"Microglia are involved in many neurological diseases, but we currently have very limited tools for selectively changing their gene expression in a living animal," Tessier said. "Our goal is to develop a platform that can be given through a conventional intravenous injection, cross the blood-brain barrier and deliver a genetic medicine directly to microglia.
"If this works as we hope, the significance goes well beyond one gene or one disease. The same basic delivery technology could potentially be paired with many different oligonucleotides to study or therapeutically control different pathways in microglia."
Colin Greineder is an associate professor of emergency medicine and pharmacology at the Medical School. His laboratory develops novel technologies to direct medicines to specific tissues and cells, with the goal of improving treatment effectiveness and reducing unwanted effects elsewhere in the body.
"The study does not assume that suppressing microglia is always beneficial," he said. "Microglia play a dual role in Alzheimer's disease. They can help remove amyloid in the early stages but cause harmful, prolonged inflammation later on. What we seek to determine with this research is when microglia activation is beneficial or harmful and control that activation in Alzheimer's disease.
"As an emergency physician, I'm particularly interested in the persistent inflammation that can follow acute brain injuries such as TBI and stroke. We think the responses of glial cells-the brain's support and immune cells-have a major influence on patients' recovery, but we lack effective tools to selectively modify those responses and understand how they shape long-term outcomes."
