Texas A&M researchers test whether a nasal spray can carry an experimental Alzheimer's drug past the brain's defenses

A pair of Texas A&M University labs is trying to get an experimental Alzheimer's medicine into the brain by way of the nose.

The project, described by Texas A&M Health on Friday, pairs neuroscientist Ashok K. Shetty, a University Distinguished Professor in the Department of Cell Biology and Genetics at the Naresh K. Vashisht College of Medicine, with Ya Wang, an associate professor in the J. Mike Walker '66 Department of Mechanical Engineering.

It is one of 11 projects picked from 112 pre-proposals for the first round of seed grants from the Texas A&M Health Dementia and Alzheimer's Research Initiative.

The work is preclinical. No patients are involved, and the researchers say any move to human trials would require far more testing of safety, dosing and effectiveness.

The drug and the delivery problem

The compound, DDL-357, is a small-molecule drug still in the experimental stage. It boosts the brain's supply of secreted clusterin, which the university describes as a protein that helps stop amyloid plaques from clinging to brain cells. Earlier animal studies linked the drug to less brain inflammation and less plaque buildup.

Shetty's lab is examining whether it can also reduce inflammation, spur new neurons and help form and protect synapses.

"Our approach is distinct, because we are targeting multiple contributing factors to cognitive decline rather than just amyloid plaque accumulation," Shetty said in the university's account.

Getting the drug where it is needed is the harder part. According to the release, the blood-brain barrier blocks about 98% of small-molecule medicines, and nearly every large-molecule one, from getting into the brain at levels that would help.

Wang's lab builds carriers from metal-organic frameworks, sponge-like porous materials whose pores can hold drug molecules. The team designed its carriers from metals the body already contains, meant to release the drug gradually and then break down. Wang said her university is one of the earliest to try these carriers for Alzheimer's treatment by nasal spray.

The idea is that a drug taken up near the top of the nasal passages can travel along nerves that run from the nose straight into the brain, sidestepping the barrier.

An earlier study by the same team gives a sense of the potential. Mice given the diabetes drug metformin through the nose in a MOF-74 carrier had roughly 9% of it arrive in the brain inside eight hours, the university says, 82 times the amount that got there when the drug was swallowed.

What comes next

The current tests will show whether enough of the drug-loaded carriers reach different parts of the brain, which cell types take them up, and whether the approach slows the disease in animals. If the early results hold up, the team plans to seek larger grants, including from the National Institutes of Health.

Shetty said slowing the disease by even a decade "would have a massive impact on patients and their families." Because most people learn they have Alzheimer's near age 80, a large enough delay could let many live out their lives before the disease takes a serious toll.

Sources

stories.tamu.edu