While ROS play a role in certain cellular functions, an excess of these molecules can lead to oxidative stress and cellular damage via an iron-dependent cell death mechanism called ferroptosis. If left unchecked, this damage can contribute to a range of serious health conditions, impacting everything from metabolic processes to neurological function.
The Challenge of Protecting Mitochondria
There are antioxidant molecules that can neutralize ROS in laboratory settings, but effectively targeting oxidative stress within mitochondria has been a challenge. Many antioxidants distribute throughout the body but fail to reach the mitochondria in sufficient quantities to offer meaningful protection.
A New Approach: Targeted Mitochondrial Protection
Our groundbreaking drug candidates address this issue directly. By specifically targeting and neutralizing ROS within the mitochondria, for instance, they help protect against oxidative damage. This novel approach not only safeguards mitochondrial health but also regulates key biological processes involved in many serious diseases, offering potential for significant therapeutic benefits.
Neurodegenerative Disorders
Mitotech is pioneering a "first-in-class" small molecule designed to specifically target and inhibit ferroptosis at its origin—within the mitochondria. By blocking ferroptosis, particularly in neurons within the central nervous system (CNS), our lead candidate SkQ1 holds promise for halting or slowing the progression of neurodegenerative diseases.
SkQ1 demonstrated efficacy in models of Friedreich’s Ataxia (FA) and Multiple Sclerosis (MS).
- Protection of FA patient fibroblasts from ferroptosis-mediated cell death in vitro using low doses of SkQ1 alone and enhanced protection in combination with omaveloxolone.
- Significantly reduced disease scores and histology inflammation scores in mouse EAE model of MS.
Metabolic diseases
Recent preclinical studies in obesity models (DIO models) demonstrated SkQ1’s potential to significantly reduce weight and enhance metabolic function, all while preserving muscle mass. The drug candidate also demonstrated a marked synergistic weight loss effect when combined with GLP-1 treatment.
- Weight reduction of 15% and fat reduction of 30% over just two weeks of treatment. Pausing SkQ1 treatment did not lead to immediate weight regain.
- Muscle mass remained largely unaffected.
- Significant synergetic weight loss efficacy in a combination with GLP-1 treatment vs both monotherapies.
In preclinical MASH models, SkQ1 treatment led to significant improvements in several key biomarkers associated with liver health and metabolic function.
- Liver triglyceride levels were significantly reduced – by 70%.
- Significant decreases in steatosis, ballooning, and fibrosis.
- Significant reduction in oxidative stress biomarkers, further supporting its role in mitigating liver damage.
Autoimmune diseases
Psoriasis is a chronic autoimmune condition characterized by inflamed, scaly patches of skin. Recent research has highlighted the role of ferroptosis in the pathogenesis of psoriasis, particularly in conjunction with the IL-23/IL-17 axis, which plays a key role in the inflammatory process.
Our lead candidate, SkQ1, has shown promising results in preclinical psoriasis models, as well as in models of other autoimmune diseases. Both topical and oral formulations of SkQ1 have demonstrated efficacy in reducing the symptoms of psoriasis, positioning it as a potential first-in-class treatment.
SkQ1 has the potential to treat psoriasis across the full spectrum of disease severity—from mild cases, typically managed with topical therapies, to more severe cases that require injectable biologics. This broad therapeutic applicability makes SkQ1 an exciting candidate for addressing the unmet needs of psoriasis patients.