MitoQ (mitoquinone) / Antipodean - LARVOL DELTA

ADVANCING A FIRST-IN-CLASS CNS-PENETRANT USP30 INHIBITOR TO INCREASE MITOPHAGY AS DISEASE MODIFYING THERAPY FOR PARKINSON'S DISEASE (ADPD 2026) - "Preclinical studies evaluated (i) cellular activity in human neural models of mitochondrial stress, (ii) in vivo engagement and enhancement of mitophagy in mitoQC reporter mice, (iii) safety, pharmacokinetics, and tolerability in IND-enabling studies. Vincere's first-in-class, oral, CNS-penetrant USP30 inhibitor restores mitochondrial quality control and has potential to be the first disease-modifying therapy targeting mitophagy in Parkinson's disease."

First-in-human • Alzheimer's Disease • CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • Targeted Protein Degradation

Oral Antioxidant Therapy Targeted to the Mitochondria for Improving Brain Artery Health in Postmenopausal Women (clinicaltrials.gov) - P=N/A | N=86 | Not yet recruiting | Sponsor: Colorado State University

New trial

Illuminating Mitochondrial RNA G-Quadruplexes as Structural Brakes on RNA Granule Assembly and OXPHOS. (PubMed, Adv Sci (Weinh)) - "Here, through rational molecular design, we developed MitoQUMA, a fluorescent probe that allows the visualization of mtRNA G4 dynamics in live cells...When RNA processing is compromised, mtRNA maturation is impaired, and MRG becomes unstable and undergoes disassembly, ultimately disrupting mitochondrial gene expression and energy metabolism. Collectively, our study introduces a tool for real-time monitoring of mtRNA G4s in cells and identifies the Wnt/β-catenin-GRSF1-mtRNA G4 axis as a previously unrecognized pathway coordinating MRG assembly and energy metabolism, providing new insights into phase separation within mitochondria."

Journal

Biomimetic scaffolds with synergistic BMSC targeting and ROS scavenging for mitochondrial protection and effective bone-defect repair. (PubMed, J Nanobiotechnology) - "Exosomes (EXOs) derived from mesenchymal stem cells have emerged as promising tools for bone repair...On MitoQ incorporation, these EXOs (EXO-MitoQ, EM) exhibit the targeted scavenging of mitochondrial reactive oxygen species; moreover, on surface decoration with the nucleic acid aptamer Apt 19 S (EM-Apt), they show the enhanced recruitment and precise delivery of BMSCs...In a rat calvarial defect model, this TCP/SIS@EM-Apt scaffold increased the BV/TV by 1.9-fold compared to TCP/SIS, due to the combination of multiple multifunctional therapeutic effects (anti-inflammatory, angiogenic, and osteogenic). The mitochondria-targeting strategy proposed in this study presents a promising solution for the reconstruction of large bone defects and offers a synergistic approach for addressing complex regenerative challenges."

Journal

Iron Overload-Induced Ferroptosis Drives Placental Dysfunction in Preeclampsia. (PubMed, Hypertension) - "Iron overload induced ferroptosis and apoptosis in trophoblasts, evidenced by increased lipid peroxidation (4HNE↑, Gpx4↓), ROS, Tunnel staining positive and cell death, while suppressing PlGF and progesterone secretion. Both deferoxamine and MitoQ rescued these effects in vitro (similar to Ferr-1) and in preeclampsia-derived organoids...Our findings reveal that iron overload and subsequent ferroptosis contribute to placental damage in preeclampsia, suggesting that iron metabolism dysregulation is a critical feature of the disease. This highlights the need to reevaluate iron supplementation protocols in high-risk pregnancies and to consider individualized iron management strategies that balance maternal-fetal iron requirements while minimizing oxidative stress."

Journal • Gynecology • Hematological Disorders • Metabolic Disorders • DMRT1 • GPX4

Natural Vitamins and Novel Synthetic Antioxidants Targeting Mitochondria in Cognitive Health: A Scoping Review of In Vivo Evidence. (PubMed, Antioxidants (Basel)) - "MTAs (MitoQ, MitoTEMPO, SS31, SkQ1) improved mitochondrial dynamics and cognitive performance and reduced dementia-related pathology. Both NVAs and MTAs improved biomarker profiles and cognitive outcomes in vivo animal models of AD and dementia, but MTAs showed more robust and consistent efficacy by directly targeting mitochondrial pathways. Given the favourable safety profiles of MTAs in other clinical conditions, early-phase human trials in dementia and AD are warranted to evaluate their long-term cognitive benefits."

Journal • Preclinical • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Metabolic Disorders

Neutrophil Extracellular Traps in Systemic Lupus Erythematosus: Pathogenic Mechanisms, Crosstalk with Oxidative Stress, and Antioxidant Therapeutic Potential. (PubMed, Antioxidants (Basel)) - "Preclinical studies show that antioxidants such as curcumin, resveratrol, and mitochondrial-targeted MitoQ reduce NET formation and ameliorate lupus nephritis; clinical trials confirm that curcumin and N-acetylcysteine (NAC) lower SLE disease activity and reduce proteinuria, supporting their role as safe adjuvant therapies. However, high-dose vitamin E may exacerbate autoimmunity, highlighting the need for dose optimization. Future research should aim to clarify the mechanisms underlying NET formation in SLE and to optimize new antioxidant therapies, including assessments of their long-term efficacy and safety."

Journal • Review • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus • DNASE1L3

Mitochondrial Dysfunction: The Cellular Bridge from Emotional Stress to Disease Onset: A Narrative Review. (PubMed, Biomolecules) - "Furthermore, we evaluate mitochondria-targeted therapeutic strategies, encompassing pharmacological compounds, such as mitoquinone mesylate, Skulachev ions, and elamipretide, alongside lifestyle and psychological interventions. Here, we aim to translate MALT biology into clinical applications, positioning mitochondrial health as a target for preventing and treating stress-related disorders. We propose that MALT may serve as a quantifiable bridge between emotional stress and somatic disease, enabling future precision medicine strategies integrating mitochondrial care."

Journal • Review • Inflammation • Metabolic Disorders • GDF15

Mitochondrial Metabolic Checkpoints in Human Fertility: Reactive Oxygen Species as Gatekeepers of Gamete Competence. (PubMed, Cells) - "Potential translational benefits can be obtained via targeted techniques that optimize mitochondrial function, such as modifying oxygen tension, employing mitochondria-directed antioxidants like MitoQ and SS-31, and supplementing with nutraceuticals like melatonin, CoQ10, and resveratrol. Understanding ROS-mediated checkpoints forms the basis for developing biomarkers of gamete competence and precision therapies to improve ART outcomes. By highlighting mitochondria as both metabolic sensors and redox regulators, this review links fundamental mitochondrial biology to clinical reproductive medicine."

Journal • Review

Pathophysiological and behavioral consequences of dichlorvos-induced oxidative stress in rodent models: A systematic review of mechanisms and protective strategies. (PubMed, Ecotoxicol Environ Saf) - "Several antioxidants, including CoQ10, MitoQ, curcumin, and quercetin, demonstrate protective efficacy by lowering ROS (45-62 %), restoring antioxidant capacity (70-90 %), and modulating apoptotic and inflammatory cascades. Collectively, this review underscores the genotoxic and neurotoxic liabilities of DDVP, highlights the therapeutic potential of antioxidant-based countermeasures, and points to critical gaps in translational relevance for agricultural health risk assessment."

Journal • Preclinical • Review • CNS Disorders • Metabolic Disorders • Movement Disorders • Pain • Parkinson's Disease

MitoQ upregulates CYP19A1 to protect dermal papilla cells from DHT-induced mitochondrial dysfunction and apoptosis in androgenetic alopecia. (PubMed, Biochem Pharmacol) - "MitoQ amplifies this cross-talk through CYP19A1 activation, restoring redox balance and mitochondrial integrity. Collectively, these results identify CYP19A1 as a pivotal regulator of mitochondrial resilience and suggest that the CYP19A1-mitochondrial axis represents a promising pharmacological target for treating AGA."

Journal • Alopecia • Immunology • Metabolic Disorders • CYP19A1 • DKK1 • IL6 • TGFB1

Targeting mitochondrial oxidative stress: A novel therapeutic strategy for degenerative joint diseases (Review). (PubMed, Biomed Rep) - "The preclinical efficacy of mitochondria-directed antioxidants (such as mitoquinone, MitoTEMPO, 10-(6'-plastoquinonyl) decyltriphenylphosphonium and Szeto-Schiller-31) in alleviating ROS-induced cellular damage, inhibiting apoptosis/pyroptosis and preserving extracellular matrix integrity in OA, IVDD and RA models were summarized...The present study identified key translational challenges (such as optimal delivery systems, long-term safety and clinical validation) and suggested integrated therapeutic frameworks that combine targeted antioxidants with advanced drug carriers and adjunctive treatments. Mitochondria-focused interventions may have potential as the next generation of disease-modifying treatments for OA, IVDD and RA."

Journal • Review • Cardiovascular • Gastroenterology • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology • PTEN • SIRT3

MARVEL: Mitochondrial Anti-oxidant Therapy to Resolve Inflammation in Ulcerative Colitis (clinicaltrials.gov) - P2 | N=79 | Active, not recruiting | Sponsor: University of Edinburgh | Recruiting ➔ Active, not recruiting | N=206 ➔ 79 | Trial completion date: Dec 2025 ➔ Nov 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Late-Onset Menopause and Attenuated Aortic Stiffness. (PubMed, Hypertension) - "Lipidomics and triglyceride-related metabolite exposure of aortas with/without the mitochondrial antioxidant MitoQ identified lipid drivers of mitochondrial reactive oxygen species-related stiffness...Triglyceride (16:0) was a driver of the effects of serum. Our findings suggest attenuated aortic stiffening via lower structural-dependent factors may be 1 mechanism by which late-onset menopause lowers cardiovascular disease risk."

Journal • Cardiovascular

SLC7A11 alleviates diquat-induced neurotoxicity by inhibiting ferroptosis and preserving mitochondrial function. (PubMed, Ecotoxicol Environ Saf) - "Furthermore, compared with monotherapy, the combination of SLC7A11 overexpression with the mitochondrial antioxidant mitoquinone mesylate (MitoQ) exhibited enhanced neuroprotective effects, resulting in superior restoration of intracellular ATP levels, mitochondrial dynamics proteins and ferroptotic marker levels. Together, these findings demonstrate that DQ induces neurotoxicity by suppressing the SLC7A11/GSH/GPX4 axis and activating ferroptosis associated with mitochondrial dysfunction. The enhancement of SLC7A11 expression, alone or in combination with mitochondrial antioxidants, has a strong neuroprotective effect, revealing SLC7A11 as a player in and therapeutic target for DQ-related neurotoxicity."

Journal • Metabolic Disorders • ACSL4 • GPX4 • SLC7A11

MITOQ MITIGATES THE EXACERBATED PRION-LIKE PROPAGATION OF TAU PATHOLOGY INDUCED BY CHRONIC CEREBRAL HYPOPERFUSION (ADPD 2026) - "These findings demonstrate that CCH aggravates tau pathology via hypoxia-induced mitochondrial dysfunction and that MitoQ mitigates tau pathology and memory impairment by preserving mitochondrial function. Our study provides experimental evidence supporting the therapeutic potential of MitoQ in the prevention and treatment of AD."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Metabolic Disorders

Mini-MARVEL - Mitochondrial Antioxidant Therapy in Ulcerative Colitis (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: University of Edinburgh | N=120 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pediatrics • Ulcerative Colitis

The Mito-Frail Trial: Effects of MitoQ on Vasodilation, Mobility and Cognitive Performance in Frail Older Adults (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: UConn Health | Trial completion date: Jul 2027 ➔ Feb 2028 | Trial primary completion date: Sep 2025 ➔ Mar 2027

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Geriatric Disorders

Müller Glial Kir4.1 Channel Dysfunction in APOE4-KI Model of Alzheimer's Disease. (PubMed, Glia) - "Our results demonstrate that APOE4 causes mitochondrial dysfunction and MC impairment, which may contribute to retinal pathology in AD. MitoQ restored mitochondrial health and Kir4.1 expression in APOE4-expressing rMC-1, suggesting targeting mitochondria may offer a promising therapeutic strategy for AD."

Journal • Alzheimer's Disease • CNS Disorders • Metabolic Disorders

SKQ1: a mitochondria-targeted antioxidant with therapeutic potential. (PubMed, J Drug Target) - "In this review, we summarize all available therapeutic evidence of SKQ1. We propose that SKQ1 represents a promising candidate for treating mitochondrial dysfunction-related diseases; however, its safety profile warrants further investigation."

Journal • Review • Metabolic Disorders

Thermotolerance induced by non-lethal heat shock at 40 °C is activated by mitochondrial ROS and is Nrf2-dependent. (PubMed, Arch Biochem Biophys) - "Mitochondrial ROS were found to be essential in mediating Nrf2-dependent thermotolerance, because MitoQ treatment prior to exposure to 40 °C reduced Nrf2 levels and dissipated the subsequent protective effect of thermotolerance against toxicity at 42 °C. Our study demonstrates that specific sources of ROS had biologically different implications in activating Nrf2, underlining potential therapeutic targets that may contribute to thermotolerance in anticancer treatments."

Journal • Oncology • NFE2L2

Mitoquinone mesylate enhances bovine oocyte in vitro maturation efficiency by modulating oxidative stress and enhancing mitochondrial function. (PubMed, Theriogenology) - "Conversely, the pro-apoptotic gene BAX was significantly downregulated (∗∗P < 0.01), whereas expression of the anti-apoptotic gene BCL-2 was significantly increased (∗P < 0.05). Collectively, these findings demonstrate that supplementation of IVM medium with 50 nmol/L MitoQ effectively alleviates OS-induced injury, enhances mitochondrial energy metabolism, and substantially improves oocyte maturation quality and subsequent embryonic developmental potential."

IO biomarker • Journal • Preclinical • BAX • BCL2 • MFN2 • SIRT3

Reprogramming the Mitochondrion in Atherosclerosis: Targets for Vascular Protection. (PubMed, Antioxidants (Basel)) - "A growing array of translational strategies-including small-molecule activators such as resveratrol and Mitoquinone (MitoQ), gene-based therapies, and nanoparticle-mediated drug delivery systems-are under active investigation. This review synthesizes current mechanistic knowledge on mitochondrial dysfunction in ASand critically appraises therapeutic approaches aimed at vascular protection through mitochondrial reprogramming."

Journal • Review • Atherosclerosis • Cardiovascular • Inflammation • Metabolic Disorders

Experimental and Clinical Approaches to Preventing Aminoglycoside-Induced Ototoxicity: A Scoping Review. (PubMed, Antioxidants (Basel)) - "(3) Preclinical evidence, encompassing in vitro and in vivo studies, delineates three principal mechanistic ways of protection: (A) antioxidant and redox modulation, including N-acetyl-L-cysteine (NAC), vitamin C, edaravone, and selected phytochemicals, which counteract reactive oxygen species-mediated hair cell apoptosis; (B) mitochondrial stabilization with compounds such as mitoquinone, celastrol, and histone deacetylase inhibitors restoring bioenergetic and proteostatic balance; and (C) restriction of aminoglycoside entry through partial blockade of the mechano-electrical transduction channel, notably by ORC-13661 and related modulators...Of the investigated pharmacologic interventions, aspirin provides the most robust and reproducible evidence of protection against gentamicin-induced hearing loss, whereas NAC demonstrates a consistent, but population-specific benefit among dialysis patients...(4) In conclusion, while experimental data establish a strong mechanistic..."

Journal • Review • Otorhinolaryngology

The Influence of Race and MitoQ Supplementation on Skin Blood Flow in the Cold (clinicaltrials.gov) - P=N/A | N=30 | Active, not recruiting | Sponsor: United States Army Research Institute of Environmental Medicine | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2025 ➔ Jan 2026

Enrollment closed • Trial completion date