Our bodies use sugar and fat from the food we consume to produce energy in our cells’ mitochondria, the internal powerhouses that give us the energy we need for all our vital functions. Over time—a lifetime—this conversion of fuel to energy causes mitochondria to accumulate free radical damage associated with the reactive oxygen species (ROS) mitochondria generate. Excess of mitochondrial ROS (mtROS) may lead to a serious disorder if left unchecked.

Although there are molecules that can neutralize ROS in vitro, protecting our mitochondria from damage by oxidative stress has traditionally been problematic because these molecules distribute throughout the body but don’t reach effective levels in the mitochondria. One of our drug candidates solves this exact problem, and by doing so it regulates downstream biological processes underlying many severe pathologies.

Neurodegenerative disorders

Ferroptosis is a recently recognized type of cell death characterized by an iron-dependent and lipid peroxidation–mediated nonapoptotic cell death. Recent studies have found that ferroptosis plays a key role in the occurrence and development of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and ALS. Mitotech is developing a “first-in-class” small molecule designed to target ferroptosis where we believe it originates – in mitochondria. By protecting mitochondrial lipids from peroxidation our lead compound aims to stop the chain reaction of ferroptosis in motor and dopaminergic neurons.


Metabolic disorders

Nonalcoholic steatohepatitis (NASH) is one of the most common chronic liver diseases, and its incidence has recently increased worldwide. Oxidative stress in mitochondria is a major component of NASH and may be a major driver of the disease. Triggered by oxidative stress, ferroptosis is considered to play an important role in initiating inflammation in NASH. Our lead drug candidate for this disease blocks peroxidation of mitochondrial lipids to stop ferroptosis and NASH development.

Despite recent breakthroughs in addressing obesity with novel drugs, mitochondrial targets of metabolic processes remain untapped. Mitotech’s lead drug candidate aims to restore metabolic processes in the body by improving mitochondrial function.