Researchers Find a Better Way to Get ALS Treatment to the Brain

Finding a promising drug to treat diseases like amyotrophic lateral sclerosis (ALS) is only half the battle. The challenge is delivering the medicine where it actually needs to go.

Antisense oligonucleotides (ASOs) are drugs that can block disease-causing signals inside cells. They hold a lot of promise for treating ALS, but the brain’s natural defenses stand in the way. The blood-brain barrier blocks them, cells struggle to absorb them, and the body often clears them out before they can do their job. Because of this, patients usually have to get these drugs injected straight into the fluid around their brain and spinal cord through a spinal tap.

Now, researchers at the University of Georgia’s Regenerative Bioscience Center (RBC) think nature already solved this delivery problem.

“Our research grew from a simple idea— instead of forcing a drug to find its way into the brain, give it a vehicle that already knows how to get there,” said Yao Yao, corresponding author of the study and an associate professor in UGA’s College of Agricultural and Environmental Sciences.

A Natural Delivery Truck

Neural stem cells naturally produce tiny, fluid-filled sacs called vesicles. These tiny sacs move molecules between cells and can cross into the nervous system.

To test the idea, the team used stem cells that produce the vesicles found in AB126, an experimental therapy from Aruna Bio that is now in clinical trials. They packed the ASO drug inside these natural carriers.

“What sets this approach apart is that the vesicles do more than deliver a therapy. They have therapeutic properties of their own. We’re harnessing both,” said Yao.

Simple Nasal Drops Instead of Injections

Instead of using spinal injections, researchers tested giving the packaged drug through the nose in mice. Nasal delivery delayed the start of the disease, improved movement, protected motor neurons, and reduced inflammation in the nervous system.

“When we packaged the ASO in these vesicles, we saw that it was more stable, reached neural tissue more effectively and stayed active longer than the ASO by itself,” said Yao.

To make sure the drug itself arrived and not just the carrier, the team tagged the medicine.

“We put a tiny marker on the ASO drug itself, not the vesicle carrying it, so we could see that it was the drug reaching the target tissue, not just the carrier,” said first author Yaochao Zheng, a doctoral student in UGA’s department of animal and dairy science. “The signal showed us which tissues and cells the treatment reached, giving us a clearer picture of its distribution.”

The team collaborated with Jie Jiang at the Emory University School of Medicine to test the approach. The work recently received funding support from the U.S. Department of Defense and the National Institutes of Health.

“The next step is to fine-tune how much treatment reaches the brain and spinal cord and test it across multiple ALS models, including human motor neurons,” said Jiang.