The ALGORITM project is an assembly of three scientific and dissemination work packages (WP) aiming to investigate the mechanisms involved in the ARDS pathophysiology in different endotypes and develop an effective personalized therapy for ARDS. We first reveal the lung tissue responses to inflammatory environments and their alterations after EV treatment at single-cell level (WP1). Our second aim was to investigate how ARDS environments alter functional properties of the alveolar epithelial-endothelial barrier and how these alterations are affected by EV treatment (WP2) as the last aim, we investigated how endotype-specific environments alter the metabolism of the primary human pulmonary cells involved in ARDS pathophysiology and how EVs alter these metabolic changes.
In WP1, Through transcriptomic analysis, it was possible to observe that the therapy has different modulatory effects, depending on the cell type, different cells have different metabolism and response, which resulted in different therapeutic responses and immunomodulation. Lung tissue has around 40 different cell types, different cells show different responses. These results will provide the development of an effective and personalized therapy aimed at the main dysfunctions and cell types involved in ARDS.
In WP2, different pharmacological therapeutic responses in patients with ARDS phenotypes, reinforcing the needed to develop a personalized therapy that can cover both phenotypes, even today there is no clinical exam that facilitates this identification. In relation to our therapy, the EVs showed beneficial effects in the Hypo phenotype, however no effects were observed in the hyper phenotype, which led us to question some modifications in the therapy: increasing the dose, multiple applications, changing routes of therapy administration. Some of these questions raised that should be answered in future research, which opened the field for the development of new therapies.
In WP3,the metabolic alterations observed in ARDS are interconnected and can create a vicious cycle, where inflammation and tissue injury further exacerbate metabolic dysfunction, leading to sustained lung injury and organ dysfunction. Understanding the metabolic changes in ARDS is important for identifying potential therapeutic targets and developing interventions that can restore metabolic homeostasis, support tissue repair, and mitigate lung injury.
Dissemination materials such as press releases, and articles have been produced. Additionally, ALGORITM has been presented at conferences, symposium and outreach activities.
