Pipeline

USP30 Inhibitor programs

Targeting USP30, a specific mitochondrial-associated DUB, with inhibitors has the potential to treat a range of rare genetic mitochondrial diseases, Idiopathic pulmonary fibrosis (IPF) as well as neurodegenerative diseases including Parkinson’s disease.

Mitochondrial dysfunction and disease

Mitochondrial dysfunction, which occurs when cells’ mitochondria do not work as well as they should, has emerged as a key factor in a multitude of diseases.

Dysfunctional mitochondria are the primary hallmark of many rare genetic mitochondrial disorders.

In addition, many age-related diseases including those that affect the nervous and metabolic system are associated with mitochondria dysfunction. These include Parkinson’s disease, Alzheimer’s disease and type 2 diabetes.

A new therapeutic target and paradigm for promoting mitophagy

USP30 inhibition

Improving the rate of mitophagy provides a novel therapeutic approach to treating mitochondrial and neurodegenerative diseases.

USP30, a specific mitochondrial-associated DUB, plays a central role in a key pathway that controls mitochondria quality and is associated with the regulation of mitophagy.

Inhibition of USP30 promotes mitophagy and therefore increases clearance and degradation of impaired mitochondria, potentially improving cellular health and longevity.

Mitophagy improves mitochondrial quality in cells: the basics

There are hundreds to several thousand mitochondria present in every cell, where they normally have a life span of approximately 40 days before they are degraded. Mitophagy is a natural process where “old” or damaged mitochondria are selectively cleared from the cell. This involves their removal by autophagosomes and subsequent degradation by lysosomes.

Mitophagy plays an essential role in keeping cells healthy, as it promotes the routine turnover of mitochondria and prevents accumulation of dysfunctional mitochondria that would otherwise induce oxidative stress within a cell and lead to cellular degeneration.

Impaired mitophagy has pathological consequences in many rare mitochondrial diseases and in neurodegeneration. The generation of dysfunctional mitochondria and the rate of mitophagy are influenced by a variety of genetic factors, such as inherited or acquired genetic mutations, and by environmental factors such as diet and stress.

Mitochondria: the basics

Mitochondria are organelles that are present in almost every cell of the human body, where they perform many essential functions. They produce about 90% of the body’s energy and many biosynthetic intermediates, as well as influencing cellular stress responses such as autophagy and apoptosis (programmed cell death). There are generally several thousand mitochondria present in each cell, with each mitochondrion normally having a life span of approximately 40 days.