One of the biggest obstacles in CMT research is not a shortage of potential therapies, but a delivery problem: nerves are extremely difficult to reach through the bloodstream. Dr. Kelly Langert’s team at Loyola University Chicago took a creative approach, asking whether the disease itself could show us a way in. In CMTX, immune cells naturally infiltrate affected nerves. Could that same pathway be used to carry a drug delivery vehicle inside?
Key Findings
The team first confirmed that immune cell infiltration into affected nerves begins as early as one month of age in CMT1X mice, earlier than previously documented. They then coated tiny polymer nanoparticles with membranes harvested from mouse immune cells, creating particles that mimic the cells the body is already sending to affected nerves.
When injected intravenously, membrane coated nanoparticles accumulated in CMT nerve tissue in both presymptomatic and symptomatic preclinical models. Uncoated nanoparticles showed negligible accumulation under the same conditions. Nanoparticles of either type showed no nerve accumulation in healthy animals, confirming the targeting is specific to the disease environment.
Learning from challenges
Getting here required patience. Both the nerve dissociation method and the nanoparticle formulation went through several rounds of refinement before producing reliable results. A key discovery along the way: monocyte membranes must be used fresh, because freeze-drying for storage destroys the surface receptors that make the targeting work. The protocols that emerged will be published as a chapter in the forthcoming third edition of “Nanoparticles in Biology and Medicine,” part of the highly cited Methods in Molecular Biology book series, for other researchers to use.
What comes next
With an established proof of concept, Dr. Langert now plans to test the approach in additional CMT mouse models and to load the nanoparticles with therapeutic cargo, moving from “we can get to affected nerves” to “we can deliver something useful.”
