A novel, first-in-its-kind, aptamer-based LYTACs to address the unmet clinical need of diabetic wounds.

ongoing

Diabetic foot ulcers (DFUs) a major complication of diabetes, occur in ~25% of patients, with a five-year recurrence rate of ~65% . DFUs often end in hospitalization, with limb amputations in up to 60% of cases . DFU related mortality is 5% within twelve months, rising to 42% after five years. Despite high prevalence and its major impact on the quality of life, no effective treatment has been approved, so DFU remain a highly unmet clinical condition. APTADEGRAD aims at obtaining in vivo proof-of-concept for a novel, first-in-class therapy using aptamer-based Lysosome Targeted Chimeras (LYTACs) to heal diabetic foot ulcers (DFUs). These LYTACs will target IL-1β, its receptor IL-1R1, and MMP-9 for degradation, proteins known to play a key role in impaired healing in diabetic wounds. Out hypothesis is that a) aptamer-based LYTACs MoA, may offer the potential to deliver a controlled, dose-dependent reduction of MMP9, IL-1b and its receptor IL-1R1, moderating the excessive DFU inflammatory response, while maintaining biologically beneficial levels of these proteins to promote healing and prevent infection; b) the simultaneous targeting of these relevant proteins will produce a synergetic effect in the inflammation cascade, providing superior efficacy outcomes. Should the main objective of the project is achieved (i.e. show efficacy in animal models of DFU), we would be showing for the first time a potential therapy based on LYTACs, in this case in the context of diabetic ulcers, with potential applications in other types of chronic wound or immune pathologies. In addition to efficacy data, we will be gathering essential knowledge about LYTACs (toxicity, efficacy, mechanism of action, differences with other approaches such as blocking or inhibition which are essential for successful future translation of the novel concept of LYTAC in pharmaceutical development to clinical trials.