Pipeline

USP30 Peripheral Indications

Disease indication

Treatment of idiopathic pulmonary fibrosis (IPF)

Mechanism of action

USP30 is a mitochondrial-associated DUB and a negative regulator of mitophagy. Inhibition of USP30 activates mitophagy, which results in increased degradation of impaired mitochondria in lysosomes.

Therapeutic Rationale

Scientific and clinical studies have demonstrated that insufficient or impaired mitophagy – a process where dysfunctional mitochondria are selectively cleared from the cell – is involved in IPF pathogenesis (Kurita et al Respiratory Research, 2017 18:114). Insufficient mitophagy in IPF has been implicated in both increasing apoptosis and cellular senescence in epithelial lung cells and enhancing fibrogenic myofibroblast differentiation in lung fibroblasts.

There is a significant unmet medical need for the treatment of IPF, as current therapies are limited to reducing certain symptoms only.

Therefore activating mitophagy through USP30 inhibition has the potential to be a promising therapeutic approach for treating IPF.

About IPF

IPF is a specific type of lung fibrosis that is a chronic and ultimately fatal disease. Over time, tissue deep in the lungs becomes scarred, resulting in a progressive decline in lung function and shortness of breath.

There are currently no cures for IPF, with the majority of people living 3 to 5 years after diagnosis.