Visomitin (plastoquinonyl decyl triphenylphosphonium) / Mitotech, BIO invest - LARVOL DELTA

Bactericidal and anti-quorum sensing activity of repurposing drug visomitin against staphylococcus aureus. (PubMed, Virulence) - "These effects were probably mediated by interfering with the S. aureus accessory gene regulator quorum sensing system. In summary, our findings suggest that Visomitin shows dual antimicrobial effects, including bactericidal effects at the concentrations above MIC and quorum sensing inhibition effects at sub-MICs, which holds promise for treating MRSA-related refractory infections."

Journal • Hematological Disorders • Infectious Disease

The mitochondrial-targeted antioxidant SkQ1 ameliorates cigarette smoke-induced oxidative stress and airway inflammation (ERS 2024) - "Aims: SkQ1 (Visomitin) is a novel mitochondrial-targeted antioxidant that effectively eliminate excessive intracellular reactive oxygen species (ROS) and holds promise in the treatment of inflammation associated diseases... SkQ1 exhibits an alleviation role in CS-induced airway inflammationand oxidative stress in vitro and in vivo, thereby playing a novel protective role in the treatment of airway disorders caused by CS."

Oxidative stress • Inflammation • Ocular Inflammation • Respiratory Diseases • IL1B • IL6 • OPA1

A Comparative Study of the Efficiency of Mitochondria-Targeted Antioxidants MitoTEMPO and SKQ1 under Oxidative Stress. (PubMed, Free Radic Biol Med) - "MitoTEMPO (MT) and Visomitin (SKQ1) are regareded as mitochondria-targeted antioxidants, which inhibit production of mitochondrial reactive oxygen species (ROS)...Subsequently, we found that MT administration in ischemic reperfusion kidney injury in mice provided superior renal protection compared to SKQ1, as evidenced by reduced plasma levels of kidney injury markers, improved renal morphology, decreased apoptosis, restored mitochondrial function, and enhanced antioxidant capacity. Overall, our findings suggest that MT is safer and has greater potential than SKQ1 as a therapeutic agent to mitigate oxidative stress damage or oxidative renal injury."

Journal • Cardiovascular • Renal Disease • Reperfusion Injury

PGC-1α/LDHA signaling facilitates glycolysis initiation to regulate mechanically induced bone remodeling under inflammatory microenvironment. (PubMed, Bone) - "The control of metabolism direction through GNE-140 and Visomitin revealed that enhanced glycolysis might act as a compensatory mechanism to resist OXPHOS-induced osteoclastogenesis by promoting osteogenesis...Notably, LDHA suppression effectively eliminated the bone repair effect mediated by PGC-1α overexpression within inflammatory mechanical environments. In conclusion, this study demonstrated a novel molecular mechanism illustrating how inflammation orchestrated glucose metabolism through glycolysis and OXPHOS to affect mechanically induced bone remodeling."

Journal • Inflammation • LDHA

Retinoprotective Effect of SkQ1, Visomitin Eye Drops, Is Associated with Suppression of P38 MAPK and ERK1/2 Signaling Pathways Activity. (PubMed, Biochemistry (Mosc)) - "Visomitin decreased phosphorylation of p38 MAPK, ERK1/2, and tau indicating suppression of activity of these MAPK signaling cascades. Thus, Visomitin eye drops are able to suppress progression of the AMD-like pathology in the OXYS rats and their effect is associated with the decrease in activity of the MAPK signaling cascades."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Mitochondria-targeted SkQ1 nanoparticles for dry eye disease: Inhibiting NLRP3 inflammasome activation by preventing mitochondrial DNA oxidation. (PubMed, J Control Release) - "Visomitin (also known as SkQ1), a mitochondria-targeted anti-oxidant, could reverse such a process by in situ scavenging of mitochondrial ROS...Results suggested that by efficiently scavenging mitochondrial ROS, SkQ1 NPs could in situ inhibit DED-induced mtDNA oxidation, thus blocking the interaction of ox-mtDNA and NLRP3; this, in turn, suppressed NLRP3 inflammasome activation and NLRP3-mediated inflammatory signaling. Results suggested that SkQ1 NPs have great potential as a new treatment for DED."

Journal • Dry Eye Disease • Inflammation • Ocular Inflammation • Ophthalmology • IL1B • NLRP3

SkQ1 Improves Immune Status and Normalizes Activity of NADPH-Generating and Antioxidant Enzymes in Rats with Adjuvant-Induced Rheumatoid Arthritis. (PubMed, Biochemistry (Mosc)) - "The aim of this work was to evaluate the effect of mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on the immune status, intensity of free radical-induced oxidation, and functioning of the antioxidant system (AOS) and NADPH-generating enzymes in rats with the adjuvant-induced RA...SkQ1 administration resulted in a dose-dependent changes in the oxidative status indicators towards the control values and normalization of the immune status parameters. SkQ1 decreased the level of mitochondrial ROS, resulting in the suppression of the inflammatory response, which might cause inhibition of free radical generation by immunocompetent cells and subsequent mitigation of the oxidative stress severity in the tissues."

Journal • Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Mitochondria-Targeted Uncouplers Decrease Inflammatory Reactions in Endothelial Cells by Enhancing Methylation of the ICAM1 Gene Promoter. (PubMed, Curr Mol Pharmacol) - "Low concentrations of mitochondrial oxidative phosphorylation uncouplers are able to increase methylation of ICAM1 gene promoter, which corresponds to the observed decrease in the levels of mRNA levels of this gene. Thus, the change in methylation of the ICAM1 gene promoter may underlie the mechanism of decreased ICAM1 expression caused by mild mitochondrial depolarization. Mitochondrial uncouplers may be exploited as possible therapeutic candidates to treat excessive inflammation in endothelium, by changing the methylation status of genomic DNA."

Journal • Cardiovascular • Inflammation • ICAM1 • TERC

Corneal Edema in Inducible Slc4a11 Knockout Is Initiated by Mitochondrial Superoxide Induced Src Kinase Activation. (PubMed, Cells) - "Slc4a11 KO-induced CE oxidative stress triggered increased Src kinase activity that resulted in perturbation of the pump components and barrier function of the CE."

Journal • CLDN1 • ER • SLC4A1 • TJP1

Penetration of Triphenylphosphonium Derivatives through the Cell Envelope of Bacteria of Mycobacteriales Order. (PubMed, Pharmaceuticals (Basel)) - "Mitochondria-targeted antioxidant and antibiotic SkQ1 (10-(plastoquinonyl)decyltriphenylphosphonium) is an excellent model for studying the penetration of substances through the bacterial cell envelope...One, but probably not the only such mechanism is a decrease in membrane potential, which is important for the implementation of many cellular processes. Thus, neither the presence of MDR pumps, nor the presence of porins, prevents the penetration of SkQ1 and CTPP through the complex cell envelope of R. fascians and M. tuberculosis."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

The Effect of Decreased SLC4A11 Expression on Lactate Efflux in Corneal Endothelial Cells (ARVO 2023) - "A novel mitochondrial-targeted antioxidant (Visomitin) is tested for its potential to reverse SLC4A11 dysregulation...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology • MCT1 • SLC4A1

Corneal edema in inducible Slc4a11 knock out is mediated by mitochondrial oxidative stress and Src Kinase activation (ARVO 2023) - "Ten µl of mitochondrial-targeted antioxidant Visomitin (1.5 µM) or Src kinase inhibitor eCF506 (1 µM) or PBS were applied to either cornea 3 times/day starting on the same day as Tm-chow feeding...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Oxidative stress • Ophthalmology • CLDN1 • ER • SLC4A1 • TJP1

Mitochondrial antioxidant SkQ1 decreases inflammation following hemorrhagic shock by protecting myocardial mitochondria. (PubMed, Front Physiol) - "The novel mitochondria-targeted antioxidant SkQ1 (Visomitin) effectively eliminate excessive intracellular ROS and exhibits anti-inflammatory effects; however, the specific role of SkQ1 in HS has not yet been explicated... HS causes damage to the rat myocardial mitochondrial structure, increases mtDNA release and ROS contents, activates the mitochondrial and ROS-related pathways, and induces systemic inflammatory response. The mitochondrial antioxidant SkQ1 can improve rat myocardial mitochondria ultrastructure, reduce mtDNA and ROS contents, and decrease inflammation by protecting myocardial mitochondria, thereby playing a novel protective role in HS."

Journal • Hematological Disorders • Immunology • Inflammation • Systemic Inflammatory Response Syndrome • IL6 • TNFA

Mitochondrial Targeted Antioxidant SKQ1 Ameliorates Acute Kidney Injury by Inhibiting Ferroptosis. (PubMed, Oxid Med Cell Longev) - "We herein investigated the effect of Visomitin (SKQ1), a novel mitochondria-targeting antioxidant, on several AKI models in vivo and in vitro. Our results revealed that SKQ1 treatment greatly reversed renal outcomes in cisplatin, ischemia-reperfusion injury (IRI), or folic acid-induced AKI models...In conclusion, SKQ1 treatment protected against ischemic- or nephrotoxic-induced AKI by inhibiting ferroptosis in vivo and in vitro. These results could facilitate a broader understanding of the interaction between mitochondrial antioxidants and ferroptotic defense mechanisms, providing a possible therapeutic strategy in AKI."

Journal • Acute Kidney Injury • Cardiovascular • Nephrology • Renal Disease • Reperfusion Injury

Electrophysiological and psychophysical studies in assessment of visual functions in patients with hereditary optic neuropathy (PubMed, Vestn Oftalmol) - "Along with VFT, OCT and color vision tests, electrophysiological studies are one of the main methods of examining patients with HON. After one year of PDTP use, there was a significant decrease in the FVEP P2 peak latency in the group with a disease duration of ≤1.5 years as of the time of treatment start. The PhNR amplitude in patients with high visual functions was found to correlate with structural changes in the ganglion cell layer and the retinal nerve fiber layer."

Journal • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

Safety and efficacy of ophthalmic mitochondrial reactive oxygen species scavenger Visomitin for the treatment of dry eye disease: findings of VISTA-1 and VISTA-2 studies (ARVO 2022) - "Visomitin ophthalmic solution, a drug designed for protecting the ocular surface from oxidative stress at mitochondrial level, demonstrated statistically significant effects on clearing of corneal staining in both VISTA-1 and VISTA-2 studies, which is a highly clinically relevant result. These findings provide support for using clearing of corneal fluorescein staining as the primary endpoint in a forthcoming pivotal study (VISTA-3).”"

Clinical • Dry Eye Disease • Ophthalmology

Effect of ophthalmic mitochondrial reactive oxygen species scavenger Visomitin® on visual acuity of patients diagnosed with Leber hereditary optic neuropathy: findings of an observational clinical study. (ARVO 2022) - "Visomitin ophthalmic solution, a drug designed for protection of ocular tissue from oxidative stress at mitochondrial level, demonstrated statistically significant improvement of BCVA relative to baseline in LHON patients. These improvements compare favorably when considering the typical natural history of disease progression. These findings warrant design of a double-masked, randomized, placebo-controlled study of Visomitin efficacy in LHON patients."

Clinical • Dry Eye Disease • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Optic Neuritis

Airborne exposure to PM10 induces corneal oxidative stress and disrupts Nrf2 mediated anti-oxidant defenses. (ARVO 2022) - "SKQ1 (Visomitin), a novel mitochondrial targeted antioxidant, was used to treat the 2 week PM10 exposed mice... Whole body PM10 exposure triggers corneal oxidative stress and disrupts the Nrf2 pathway which regulates antioxidant defenses. SKQ1 treatment reverses these deleterious effects. In vitro corneal epithelial cell data parallel the in vivo effects, suggesting human applicability."

Ophthalmology

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease. (PubMed, Acta Pharm Sin B) - "As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus

VISTA-2: Vehicle-Controlled Study of SkQ1 as Treatment for Dry-eye Syndrome (clinicaltrials.gov) - P3; N=610; Completed; Sponsor: Mitotech, SA; Active, not recruiting ➔ Completed

Clinical • Trial completion • Dry Eye Disease • Ophthalmology

Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators. (PubMed, Antioxidants (Basel)) - "Rats with experimental diabetes induced by the intraperitoneal injection of alloxan were subjected to the antioxidant pre-therapy with a series of mitochondria-targeted 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) injections and analyzed for the expression of mRNAs and microRNAs by real-time quantitative polymerase chain reaction to identify potential predictors of diabetes...Mitochondria-targeted antioxidant SkQ1 demonstrates positive effects on several levels, from the normalization of the blood glucose content to genetic and epigenetic changes. Our results can serve as a basis for the development of novel therapeutic and diagnostic strategies."

Journal • Diabetes • Metabolic Disorders • PCR

Dry eye: What’s in the pipeline? (Review of Optometry) - "Francis Mah, MD...is intrigued by the drug’s mechanism of action. 'I think it’s really unique in that you’re potentially stimulating all three sources or layers of the tear film,' he says....There are several new cyclosporine products in various stages of development. According to John Sheppard, MD, who is in practice in Norfolk, Virginia, Novaliq is investigating two products based on the company's semifluorinated alkane water-free vehicle. 'They've come up with the first truly new vehicle [EyeSol] for topical eye medications in over a generation,' Dr. Sheppard says....Dr. Sheppard says that the beauty of looking at both osmolarity and MMP-9 is that the osmolarity acts as a normalizing comparator to further refine the accuracy of the MMP-9 test."

Media quote

MEK1/2-ERK Pathway Alterations as a Therapeutic Target in Sporadic Alzheimer's Disease: A Study in Senescence-Accelerated OXYS Rats. (PubMed, Antioxidants (Basel)) - "Previously, using senescence-accelerated OXYS rats, which simulate key characteristics of the sporadic AD type, we have shown that prolonged treatment with mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1) during active progression of AD-like pathology improves the activity of many signaling pathways (SPs) including the p38 MAPK SP...SkQ1 decreased hyperphosphorylation of tau protein, which is present in pathological aggregates in AD. Thus, SkQ1 alleviates AD pathology by suppressing MEK1/2-ERK1/2 SP activity in the OXYS rat hippocampus and may be a promising candidate drug for human AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • MAP2K1 • MAP2K2

Antioxidants resveratrol and SkQ1 attenuate praziquantel adverse effects on the liver in Opisthorchis felineus infected hamsters. (PubMed, Acta Trop) - "The combination of PZQ with resveratrol (RSV) or 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) significantly reduced hepatocyte changes (P = 0.009 and P = 0.009, respectively, Mann-Whitney U test) as compared with infected hamsters treated only with PZQ. The combinations of the anthelmintic drug with antioxidants RSV and SkQ1 ameliorate host oxidative stress and mitigate adverse effects of PZQ on hepatic parenchyma. The use of drug combinations may improve the action of standard anthelmintic agents, such as PZQ, which still remains the most effective agent against adult trematodes."

Adverse events • Journal • Fibrosis • Immunology • Infectious Disease • Inflammation

Anthelmintic Activity of Antioxidants: In Vitro Effects on the Liver Fluke Opisthorchis felineus. (PubMed, Pathogens) - "The mitochondria-targeted antioxidant SkQ1 [10-(6'-plastoquinonyl)decyltriphenylphosphonium] in motility assays was as effective (half-maximal inhibitory concentration [IC] 0.6-1.4 μM) as praziquantel (IC 0.47-1.4 μM), and SkQ1 was significantly more effective than praziquantel in mortality assays. Results of our study indicate that SkQ1 and flavonoids have high anthelmintic activities against the liver flukes. We propose that structure-activity relationship research might be worthwhile based on the structures of the most effective substances."

Journal • Preclinical