Project Portugal 2030

Summary

MiDISC has the ambition of delivering a minimally invasive personalized immunotherapy for LDH, by combining prognosis and therapy, which is essential to tackle such a complex condition with a high intrinsic patient variability. The overarching aims of MiDISC are 1) To identify new clinical prognostic biomarkers of spontaneous LDH regression and 2) To validate preclinically a macrophage-based immunotherapy for LDH regression. These two goals are independent but integrative: by stratifying LDH patients based on prognostic biomarkers, clinicians will be able to identify those patients that do not have the intrinsic ability to naturally resorb their hernias and which should be indicated to receive the macrophage-based immunotherapy (Figure 1). This will be achieved through the following specific objectives (SO): SO#1: Patients enrolment and follow-up. LDH patients will be enrolled in the study and will be clinically and radiologically followed for assessment of spontaneous hernia regression and tissue collection. SO#2: Identify prognostic biomarkers of LDH regression. We will use clinical and proteomic data to identify non-invasive circulating predictive markers for anticipating LDH regression. This prognostic tool will be crucial for patient management, aiding in the clinical decision on conservative versus surgical treatment, stratifying the patients and opening the door to personalized medicine for LDH. SO#3: Identify a macrophage phenotype that is pro-phagocytic of LDH tissue. By performing phagocytosis assays with clinical hernia explants, the most promising macrophage phenotype will be identified with enhanced therapeutic potential towards LDH regression. SO#4: Develop an injectable biomimetic hydrogel for in situ macrophage delivery An injectable hydrogel will be developed capable of encapsulating and delivering macrophages. The developed delivery system seeks to provide a controlled and targeted release of macrophages to the herniated tissue, facilitating their therapeutic action. SO#5: Demonstrate preclinical efficacy and safety of MiDISC therapy Through rigorous preclinical testing, MiDISC therapy will be validated in a clinically relevant rat model to demonstrate the potential translatability of the therapy to human patients. SO#6 Maximize MiDISC clinical translation Results from MiDISC will be exploited to facilitate clinical translation and maximize the societal and economic impacts.