Topical 4-AP gel promising for burn wound closure

Second-degree burn wound after two days of healing. Phot by Cjr80 via Wikimedia Commons

A topical gel formulation of 4-aminopyridine (4-AP) for the treatment of burn wounds has achieved near-complete closure within 21 days in animal models. The findings were published in the journal Biomaterials.

Researchers at the Terasaki Institute for Biomedical Innovation and the University of Arizona College of Medicine have developed the new formulation. The medication is best known under the brand name Ampyra, which is indicated for the treatment of multiple sclerosis.

In a press release, the authors note that earlier research showed 4-AP could influence keratinocytes and fibroblasts. However, systemic administration carried unacceptable risks. Prolonged systemic use of 4-AP can cause serious side effects, including seizures, making localized delivery a critical advance. Embedding it in a gel resolves that problem while preserving its therapeutic potential.

The new laponite-gelatin gel delivers 4-AP directly to the wound, concentrating the medication where it is needed rather than exposing the whole body to it.

This research offers a non-invasive alternative to the current gold standard for burn wounds: autologous skin grafting.

“By delivering 4-AP directly to the wound site, we harness its regenerative potential while avoiding the systemic risks that have limited its use. We believe this approach could meaningfully change how burn injuries are managed clinically,” said Dr. Johnson V. John, Assistant Professor at the Terasaki Institute for Biomedical Innovation, in the release.

Laboratory tests confirmed that the gel releases 4-AP at a controlled rate, is compatible with living cells, and produces more than 90% wound closure within 48 hours. In animal studies, treated wounds closed faster than controls starting at day six, reaching near-complete closure by day 21, while control wounds remained partially open. Tissue analysis showed the gel reduced inflammation, promoted re-epithelialization and angiogenesis, and drove fibroblast-to-myofibroblast transformation. Collagen deposition increased markedly by 438% for type I and 288% for type III collagen versus controls (p<0.05 to p<0.0002), with an improved collagen ratio signalling better-quality tissue maturation.

Because 4-AP is already approved by the U.S. Food and Drug Administration and has a well-characterized safety profile, this repurposing strategy could accelerate the path to clinical trials compared with developing an entirely new compound from scratch.

“This research exemplifies our commitment to reimagining existing therapies to address medicine’s most persistent challenges. We look forward to seeing it advance toward clinical application,” stated Xiling Shen, Acting Director of the Terasaki Institute for Biomedical Innovation.