Skulachev 2013 Abstract MiP2013
Skulachev VP (2013) SkQ1, the first mitochondria-targeted medicine available in drugstores. Mitochondr Physiol Network 18.08. |
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MiP2013, Book of Abstracts Open Access
Skulachev VP (2013)
Event: MiPNet18.08_MiP2013
βOne can qualify himself as a physiologist only if he succeeded in normalizing a physiological process damaged by a pathologyβ (IP Pavlov)
In this group, a concept was put forward considering mitochondrial reactive oxygen species (mtROS) as key intermediates of programmed aging of organism. As a consequence of such a concept, it was suggested that aging program can be retarded (or even switched off) by mitochondria-targeted antioxidants [5]. To this end, 10-(6β-plastoquinonyl) decyltriphenyl phosphonium cation (SkQ1) was synthesized. It was shown that SkQ1 (i) is good penetrant for model and mitochondrial membranes, (ii) has very high affinity to membranes, (iii) is reduced by center i of respiratory Complex III in the inner leaflet of the inner mitochondrial membrane, (vi) electrophoretically accumulates in this leaflet, being driven by the mitochondrial membrane potential, (v) prevents peroxidation of mitochondrial cardiolipin by mtROS, (vi) arrests the ROS-induced apoptosis and necrosis, (vii) prolongs the lifespan of various organisms (from fungi and plants to mammals), and (viii) retards development of many traits of age-related diseases [1-6]. In particular, it was found that drops of SkQ1 instillated to eyes of rats prevent aging of tear glands, an effect leading to cure of such a disease as the dry eye syndrome which is usually assumed to be incurable and can result in uveitis. Clinical trials of drops of 250 nM SkQ1 solution called βVisomitinβ showed that the three-week treatment (3 drops per day) completely cure the dry eye syndrome in 60% patients. The following favorable changes were shown: an increase in the amount of tears, stability of tear film, acuity of vision as well as disappearance of inflammation in the eye tissues [7]. Drops of Visomitin are available in drugstores of Moscow and other places of Russia since July, 2012. By May 12, 2013, about 50 000 samples of the SkQ1 drops were sold and no claims concerning an unfavorable side effect were sent to the producers. Clinical trials of Visomitin as potential medicine to treat two other age-related eye diseases, namely cataract and glaucoma, were completed. For one of them (cataract), results are already available. In particular, it was found that acuity of vision was increased in 80.5% cataract patients β₯ 70 years.
Preclinical trials of SkQ1 in treatment of the dry eye syndrome and uveitis were originally performed in Russia and are now confirmed in three laboratories in the USA (Ora Inc., Andover; Toxikon Corp., Minneapolis; Comparative Biosciences Inc., Sunny Vale). In the next future, clinical trials of Visomitin will start in the USA.
β’ Keywords: Eye, model membranes, Antioxidant, necrosis, Dry eye syndrome, uveitis, cataract, glaucoma
β’ O2k-Network Lab: RU Moscow Skulachev VP
Labels: MiParea: Respiration, Genetic knockout;overexpression, Comparative MiP;environmental MiP, mt-Medicine, Pharmacology;toxicology Pathology: Aging;senescence, Alzheimer's, Cancer, Cardiovascular, Infectious, Myopathy, Neurodegenerative, Other Stress:Ischemia-reperfusion, Oxidative stress;RONS Organism: Human, Mouse, Horse, Dog, Rabbit, Fishes, Other invertebrates, Fungi, Plants Tissue;cell: Heart, Skeletal muscle, Nervous system, Kidney, Islet cell;pancreas;thymus, Other cell lines, HeLa, Fibroblast, Stem cells Preparation: Intact organism, Intact cells, Isolated mitochondria, SMP
Regulation: mt-Membrane potential, Threshold;excess capacity, Uncoupler Coupling state: LEAK, ET
HRR: Oxygraph-2k, TPP
MiP2013
Affiliations and author contributions
Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Russia. - Email: [email protected]
Preclinical trials of SkQ1 in treatment of the dry eye syndrome and uveitis were originally performed in Russia and are now confirmed in three laboratories in the USA (Ora Inc., Andover; Toxikon Corp., Minneapolis; Comparative Biosciences Inc., Sunny Vale). In the next future, clinical trials of Visomitin will start in the USA.
References
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