Researchers Advance Novel Therapy for Hard-to-Heal Diabetic Foot Wounds

Diabetic foot ulcers are chronic, hard-to-heal wounds that arise in people with diabetes and increase the risk of infection, hospitalization, and amputation. Care often relies on cleaning and dressing, which can control symptoms but do not correct the inflammatory biology that prevents wound closure. The burden is substantial for patients and health systems, as ulcers frequently recur and mortality rises when healing fails. In response, researchers have developed a therapeutic approach that targets inflammatory proteins considered key drivers of non-healing diabetic wounds.

The approach, developed within the APTADEGRAD project, uses lysosome-targeting chimeras (LYTACs) to remove excess inflammatory proteins from diabetic wounds. Lincbiotech, a Spanish biotechnology company, coordinates the project. The aim is to provide a disease-modifying therapy for diabetic foot ulcers rather than symptomatic wound care.

LYTACs are bifunctional molecules that bind a target protein while engaging receptors on the cell surface to trigger endocytosis. In diabetic wounds, the targets include interleukin-1 beta (IL-1β), its receptor IL-1R1, and matrix metalloproteinase-9 (MMP-9), which can accumulate to levels that interfere with normal healing. After internalization, the resulting complex is delivered to the lysosome, where both the drug and the captured protein are degraded. This process reduces pathological inflammation while preserving the protein levels needed for tissue repair.

In preclinical diabetic wound models, the LYTAC-based compounds accelerated wound closure and reduced inflammatory activity. Their performance was often comparable to or better than antibody therapies that block protein function without removing the target itself. To support local administration, the team has designed two delivery formats: subcutaneous injections placed near the ulcer and a hydrogel that gradually releases the agents onto the wound surface.

Diabetic foot ulcers remain a major complication, affecting about a quarter of the more than 800 million people with diabetes worldwide. Mortality approaches 5% within one year of ulcer onset and rises to 42% within five years, underscoring the need for therapies that address disease mechanisms. The project is scheduled to run until 2027, with the next milestone focused on building safety and efficacy data to enable human clinical trials that are anticipated around 2030. The same platform may extend to other chronic wounds and inflammatory diseases.

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