Scientists from Wake Forest University, Duke University, and the University of Wisconsin-Madison announced on Apr. 16 new research that could lay the groundwork for gene therapies to regrow human limbs. The team studied a common gene in salamanders, mice, and zebrafish to identify genetic programs that drive regeneration.
The potential impact of this research is significant because more than one million limb amputations occur worldwide each year due to vascular diseases, injuries, cancer, or infections. With an aging population and rising diabetes diagnoses, this number is expected to increase further.
“This significant research brought together three labs, working across three organisms to compare regeneration,” said Josh Currie, Assistant Professor of Biology at Wake Forest University. “It showed us that there are universal, unifying genetic programs that are driving regeneration in very different types of organisms, salamanders, zebrafish and mice.” The scientists focused on SP genes—specifically SP6 and SP8—which they found are vital for limb regeneration across all three species.
Using CRISPR gene-editing technology in his lab’s axolotl studies, Currie reported that removing the SP8 gene prevented proper limb bone regrowth. Similar results were observed with mouse digits missing both SP6 and SP8. Collaborators then developed a viral gene therapy using a tissue enhancer from zebrafish to deliver FGF8—a molecule usually activated by SP8—to encourage digit bone regrowth in mice.
Currie explained the broader significance: “We can use this as a kind of proof of principle that we might be able to deliver therapies to substitute for this regenerative style of epidermis in regrowing tissue in humans.” He also noted that while much more research is needed before moving from mouse digits to human limbs, these findings represent foundational progress toward therapies for limb loss after injury or disease.
Looking ahead at future possibilities and collaboration among researchers studying different animals Currie said: “A real standout feature of this research is that we work across all these different organisms. That is really powerful, and it’s something that I hope we’ll see more of in the field.”
