Researchers have identified the previously uncharacterized microtubule-severing enzyme, Fidgetin-like 2 (FL2), as a potential therapeutic target for regenerating and repairing cutaneous wounds. FL2, according to the new study's authors, is “a fundamental regulator of cell migration that can be targeted in vivo using nanoparticle-encapsulated siRNA to promote wound closure and regeneration.”
They found, in vitro, FL2 depletion from mammalian tissue culture cells increased cell movement rate by more than two-fold. The researchers clinically translated their findings by locally depleting FL2 in murine full-thickness excisional and burn wounds. That’s where they found that topical application of FL2 siRNA nanoparticles to either wound type significantly improved the rate and quality of wound closure--clinically and histologically--relative to controls.
DT: How does Fidgetin-Like 2 differ as a therapeutic target in wound healing?
Charafeddine: When we started working on this, we noticed that most of the therapeutic targets were components of complex extracellular signaling pathways. These targets might have potent effects on wound healing, but they can also result in numerous unintended and difficult to predict side effects because these pathways alter cell behavior on so many different levels. With FL2, we have an intracellular target that specifically affects a subset of the cell’s structural migration machinery. Instead of flooding the system with regenerative and proliferative agents, we are fine tuning it for a more productive healing without changing the broader signaling milieu within the wound.