Texas A&M EV nasal spray suppresses NLRP3 and cGAS-STING after two doses in aged rodents

Researchers at Texas A&M delivered EVs enriched with specific microRNAs via nasal spray to 18- and 22-month-old mice. The vesicles reached microglia within hours, downregulated NLRP3 and cGAS-STING transcripts, lowered IL-1β protein levels, and increased mitochondrial respiratory capacity measured by Seahorse assay. Memory performance returned to levels recorded in 6-month-old controls within 14 days and remained stable at 90-day follow-up.

The Journal of Extracellular Vesicles paper reports consistent outcomes across sexes and no detectable peripheral cytokine elevation. Intranasal biodistribution showed 4.2-fold higher EV signal in brain versus intravenous route at 6 hours. Prior intranasal stem-cell EV studies in stroke models achieved only transient 30-day effects; the current cargo selection targets upstream inflammasome nodes rather than broad anti-inflammatory cytokines.

Operational deployment would require GMP-grade EV production at scale and confirmation that human nasal epithelium permits equivalent microRNA transfer. Regulatory path likely begins with safety studies in mild cognitive impairment cohorts rather than healthy aging, given existing FDA guidance on intranasal biologics. No data yet address whether repeated dosing is needed after the initial two-dose window.

Next milestones include publication of dose-response curves in larger mammals and filing of an IND application once toxicology packages clear.