Use of MicroRNAs in the Treatment of Lung Diseases

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease causing chronic respiratory failure. In IPF, alveolar type II cells (ATIIs) are damaged and therefore cannot trans-differentiate to alveolar type I cells (ATIs), ATII to ATI trans-differentiation is an essential physiological process for effective alveolar repair after damage. Thus, ATII cells represent a relevant target for the development of new pro-regenerative therapies for the lung. We successfully identified microRNAs regulating ATII to ATI trans-differentiation. Specifically, our aim is to leverage these microRNAs to restore the natural regenerative capacity of human lungs, thereby mitigating the abnormal fibrotic response typically observed following chronic and acute alveolar damage. This therapeutic strategy holds potential not only for IPF but also for other lung diseases characterized by impaired lung repair mechanisms.

Can be used as treatment and/or prevention of lung pathological conditions
Can be used in promoting lung regeneration in a subject with a lung condition

Progressive fibrosing interstitial lung disease occurs when alveolar regeneration is impaired due to the inability of alveolar type II cells (ATIIs) to trans-differentiate into alveolar type I cells (ATIs). Therefore, ATII to ATI trans-differentiation process represents a relevant target for the development of innovative regenerative therapy for the human lung. In this perspective, we phenotypically screened 2042 human microRNAs on primary murine ATIIs looking for microRNAs regulating ATIIs to ATIs trans-differentiation in primary mouse ATII cells. Following this approach, we selected a number of miRNAs promoting and blocking ATIIs to ATIs trans-differentiation. All selected microRNAs were further characterized and resulted safe by showing no pro-tumorigenic effect in vitro on A549 cells, by not showing any pro-fibrotic phenotype in primary mouse alveolar fibroblasts. Last, one of the selected microRNAs, if formulated as an AAV-vector, showed efficacy in the bleomycin-induced mouse model of lung fibrosis in both prophylactic and therapeutical conditions.

Prevention/treatment of lung diseases.
Prevention/treatment of interstitial lung diseases.
Pharmaceutical sector.