Skulachev 2013 Abstract MiP2013

From Bioblast
Jump to: navigation, search
Skulachev VP (2013) SkQ1, the first mitochondria-targeted medicine available in drugstores. Mitochondr Physiol Network 18.08.
Link:
Vladimir Skulachev
MiP2013, Book of Abstracts Open Access

Skulachev VP (2013)

Event: MiPNet18.08_MiP2013

“One can qualify himself as a physiologist only if he succeeded in normalizing a physiological process damaged by a pathology” (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-(6’-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 “Visomitin” 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 ≥ 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.

Keywords: Eye, model membranes, Antioxidant, necrosis, Dry eye syndrome, uveitis, cataract, glaucoma

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: skulach@belozersky.msu.ru

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

  1. Antonenko YN, Avetisyan AV, Cherepanov DA, Knorre DA, Korshunova GA, Markova OV, Ojovan SM, Perevoshchikova IV, Pustovidko AV, Rokitskaya TI, Severina II, Simonyan RA, Smirnova EA, Sobko AA, Sumbatyan NV, Severin FF, Skulachev VP (2011) Derivatives of rhodamine 19 as mild mitochondria-targeted cationic uncouplers. J Biol Chem 286: 17831-40.
  2. Severin FF, Severina II, Antonenko YN, Rokitskaya TI, Cherepanov DA, Mokhova EN, Vyssokikh MY, Pustovidko AV, Markova OV, Yaguzhinsky LS, Korshunova GA, Sumbatyan NV, Skulachev MV, Skulachev VP (2010) Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore. Proc Natl Acad Sci USA 107: 663-8.
  3. Skulachev MV, Antonenko YN, Anisimov VN, Chernyak BV, Cherepanov DA, Chistyakov VA, Egorov MV, Kolosova NG, Korshunova GA, Lyamzaev KG, Plotnikov EY, Roginsky VA, Savchenko AY, Severina II, Severin FF, Shkurat TP, Tashlitsky VN, Shidlovsky KM, Vyssokikh MY, Zamyatnin AA, Zorov DB, Skulachev VP (2011) Mitochondrial-targeted plastoquinone derivatives. Effect on senescence and acute age-related pathologies. Curr Drug Targ 12: 800-826.
  4. Skulachev VP, Anisimov VN, Antonenko YN, Bakeeva LE, Chernyak BV, Erichev VP, Filenko OF, Kalinina NI, Kapelko VI, Kolosova NG, Kopnin BP, Korshunova GA, Lichinitser MR, Obukhova LA, Pasyukova EG, Pisarenko OI, Roginsky VA, Ruuge EK, Senin II, Severina II, Skulachev MV, Spivak IM, Tashlitsky VN, Tkachuk VA, Vyssokikh MY, Yaguzhinsky LS, Zorov DB (2009) An attempt to prevent senescence: a mitochondrial approach. Biochim Biophys Acta 1787: 437-61.
  5. Skulachev VP, Antonenko YN, Cherepanov DA, Chernyak BV, Izyumov DS, Khailova LS, Klishin SS, Korshunova GA, Lyamzaev KG, Pletjushkina OY, Roginsky VA, Rokitskaya TI, Severin FF, Severina II, Simonyan RA, Skulachev MV, Sumbatyan NV, Sukhanova EI, Tashlitsky VN, Trendeleva TA, Vyssokikh MY, Zvyagilskaya RA (2010) Prevention of cardiolipin oxidation and fatty acid cycling as two antioxidant mechanisms of cationic derivatives of plastoquinone (SkQs). Biochim Biophys Acta 1797: 878-89.
  6. Plotnikov EY, Morosanova MA, Pevzner IB, Zorova LD, Manskikh VN, Pulkova NV, Galkina SI, Skulachev VP, Zorov DB (2013) Protective effect of mitochondria-targeted antioxidants in an acute bacterial infection. PNAS (accepted).
  7. Yani EV, Katargina LA, Chesnokova NB, Beznos OV, Savchenko AY, Vygodin VA, Gudkova EY, Jn. ZAA, Skulachev MV (2012) The first experience of using the drug Vizomitin in the treatment of "dry eyes" Pract Med 4: 134-137 (Russ.).