References

medgen

Медицинская генетика

Medical Genetics

2073-7998

Publishing House «Genius Media» LLC

medgen-195

Research Article

НАУЧНЫЕ ОБЗОРЫ

REVIEW

Современные подходы к лечению миодистрофий

Current approaches for treatment of muscular dystrophies

Вяхирева

Ю. В.

Vyakhireva

J. V.

noemail@neicon.ru

Зернов

Н. В.

Zernov

N. V.

noemail@neicon.ru

Марахонов

А. В.

Marakhonov

A. V.

noemail@neicon.ru

Гуськова

А. А.

Guskova

A. A.

noemail@neicon.ru

Скоблов

М. Ю.

Skoblov

M. Yu.

mskoblov@generesearch.ru

Федеральное государственное бюджетное научное учреждение «Медико-генетический научный центр»РоссияResearch Center for Medical GeneticsRussian Federation

Федеральное государственное бюджетное научное учреждение «Медико-генетический научный центр»; Московский физико-технический институтРоссияResearch Center for Medical Genetics; Moscow Institute of Physics and TechnologyRussian Federation

Федеральное государственное бюджетное научное учреждение «Медико-генетический научный центр»; Московский физико-технический институт; Московский государственный медико-стоматологический университет им. А.И. ЕвдокимоваРоссияResearch Center for Medical Genetics; Evdokimov Moscow Medical Stomatological UniversityRussian Federation

2016

30012017

1510316

2017

Вяхирева Ю.В., Зернов Н.В., Марахонов А.В., Гуськова А.А., Скоблов М.Ю.

Vyakhireva J.V., Zernov N.V., Marakhonov A.V., Guskova A.A., Skoblov M.Y.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.medgen-journal.ru/jour/article/view/195

Мышечные дистрофии представляют собой группу генетически обусловленных нервно-мышечных заболеваний, характеризующихся нарастающей мышечной слабостью и дегенерацией мышц. Наиболее распространенные из них - миодистрофия Дюшенна (МДД) и лице-плече-лопаточная дистрофия Ландузи-Дежерина (МЛД). К настоящему времени патогенез данных заболеваний достаточно хорошо изучен, что позволяет разрабатывать различные терапевтические подходы. Некоторые препараты для терапии МДД прошли все стадии клинических испытаний, одобрены медицинскими ассоциациями и применяются для лечения больных. В случае же МЛД, кардинально отличающейся своим патогенезом, терапевтические подходы только разрабатываются. Появившиеся в последнее время молекулярные и клеточные технологии в совокупности с пониманием патогенеза данного заболевания позволяют надеяться на скорый успех в данной области.

Muscular dystrophies are the group of hereditary neuromuscular disorders characterized by progressive musclular weakness and degeneration of muscles. The most common of them are Duchenne muscular dystrophy (DMD) and Landouzi-Dejerine facioscapulohumeral muscular dystrophy (FSHD). To date, the pathogenesis of these diseases is well studied that allow to develop various therapeutic approaches for the treatment. Several drugs for the Duchenne muscular dystrophy get through all stages of clinical trials approved by FDA (food drug administration) and are utilized for treatment. Pathogenesis of FSHD differs substantially from DMD, and therapeutic approaches are only under development. Molecular and cellular technologies as well as the understanding of the disease pathogenesis allow to hope for a quick success in this area.

миодистрофия Дюшеннамиодистрофия ЛандузиДежеринапатогенез заболеваниятерапия моногенных заболеванийDuchenne muscular dystrophyLandouzy-Dejerine facioscapulohumeral muscular dystrophypathogenesis of the diseasetherapy of monogenic diseases

References1

Emery, A.E., The muscular dystrophies. Lancet, 2002. 359(9307): p. 687-95.

Chung, J. et al. Twenty-year follow-up of newborn screening for patients with muscular dystrophy. Muscle Nerve, 2016. 53(4): p. 570-8.

E, M., On fatty degeneration of the voluntary muscles: report of the Royal Medical and Chirurgical Society. 1851. 2: p. 588-89.

E., M., On granular and fatty degeneration of the voluntary muscles. Medico-Chirurgical Trans, 1852. 35: p. 73-84.

Emery AEH, E.M., The history of a genetic disease: Duchenne muscular dystrophy or Meryon’s disease. London: Royal Society of Medicine Press, 1995.

GBA., D., Case 68: Paraplegie cerebrale, congenitale, hypertrophique. L’Electrisation localisee et de son application a la pathologie et a la therapeutique, 2nd edn. Paris: J-B Bailliere et Fils, 1861: p. 354-56.

GBA., D., Recherches sur la paralysie musculaire pseudohypertrophique ou paralysie myo-sclerosique. Archives Generales Medecine 1868. 11: p. 5-25, 179-209, 305-21, 421-43, 552-88.

Muntoni, F.T., S.; Ferlini, A., Dystrophin and mutations: One gene, several proteins, multiple phenotypes. Lancet Neurol., 2003. 2: p. 731-740.

Hoffman, E.P., R.H. Brown, Jr., and L.M. Kunkel, Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell, 1987. 51(6): p. 919-28.

Cirak, S. et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet, 2011. 378(9791): p. 595-605.

Ogura, Y. et al. Therapeutic potential of matrix metalloproteinases in Duchenne muscular dystrophy. Front Cell Dev Biol, 2014. 2: p. 11.

Kim, T.W., K. Wu, and I.B. Black, Deficiency of brain synaptic dystrophin in human Duchenne muscular dystrophy. Ann Neurol, 1995. 38(3): p. 446-9.

Guiraud, S. et al. Advances in genetic therapeutic strategies for Duchenne muscular dystrophy. Exp Physiol, 2015. 100(12): p. 1458-67.

Ferlini, A., M. Neri, and F. Gualandi, The medical genetics of dystrophinopathies: molecular genetic diagnosis and its impact on clinical practice. Neuromuscul Disord, 2013. 23(1): p. 4-14.

Falzarano, M.S. et al. Duchenne Muscular Dystrophy: From Diagnosis to Therapy. Molecules, 2015. 20(10): p. 18168-84.

Falzarano, M.S., C. Passarelli, and A. Ferlini, Nanoparticle delivery of antisense oligonucleotides and their application in the exon skipping strategy for Duchenne muscular dystrophy. Nucleic Acid Ther, 2014. 24(1): p. 87-100.

van Westering, T.L., C.A. Betts, and M.J. Wood, Current understanding of molecular pathology and treatment of cardiomyopathy in duchenne muscular dystrophy. Molecules, 2015. 20(5): p. 8823-55.

Drachman, D.B., K.V. Toyka, and E. Myer, Prednisone in Duchenne muscular dystrophy. Lancet, 1974. 2(7894): p. 1409-12.

Goemans, N. and G. Buyse, Current treatment and management of dystrophinopathies. Curr Treat Options Neurol, 2014. 16(5): p. 287.

Griggs, R.C. et al. Corticosteroids in Duchenne muscular dystrophy: major variations in practice. Muscle Nerve, 2013. 48(1): p. 27-31.

Nayak, S. and B. Acharjya, Deflazacort versus other glucocorticoids: a comparison. Indian J Dermatol, 2008. 53(4): p. 167-70.

Bonifati, D.M.R., G.; Bonometto, P.; Berardinelli, A.; Gorni, K.; Orcesi, S.; Lanzi, G.; Angelini, C., A multicenter double-blind randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Muscle Nerve, 2000. 23: p. 1344-1347.

Escolar, D.M. et al. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology, 2011. 77(5): p. 444-52.

Griggs, R.C. et al. Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months). Neurology, 1993. 43(3 Pt 1): p. 520-7.

Mendell, J.R. et al. Randomized, double-blind six-month trial of prednisone in Duchenne’s muscular dystrophy. N Engl J Med, 1989. 320(24): p. 1592-7.

Mesa, L.E.D., A.L.; Corderi, J.; Marco, P.; Flores, D., Steroids in Duchenne muscular dystrophy-deflazacort trial. Neuromuscular. Disord., 1991. 1: p. 261-266.

Balaban, B. et al. Corticosteroid treatment and functional improvement in Duchenne muscular dystrophy: long-term effect. Am J Phys Med Rehabil, 2005. 84(11): p. 843-50.

Biggar, W.D.H., V.A.; Eliasoph, L.; Alman, B., Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul. Disord., 2006. 16: p. 249-255.

King, W.M. et al. Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology, 2007. 68(19): p. 1607-13.

Merlini, L. et al. Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up. Muscle Nerve, 2012. 45(6): p. 796-802.

Heier, C.R.D., J.M.; Yu, Q.; Dillingham, B.C.; Huynh, T.; van der Meulen, J.H.; Sali, A.; Miller, B.K.; Phadke, A.; Scheffer, L.; et al., VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol. Med., 2013. 5: p. 1569-1585.

Seto, J.T., N.E. Bengtsson, and J.S. Chamberlain, Therapy of Genetic Disorders-Novel Therapies for Duchenne Muscular Dystrophy. Curr Pediatr Rep, 2014. 2(2): p. 102-112.

Guiraud, S. et al. The Pathogenesis and Therapy of Muscular Dystrophies. Annu Rev Genomics Hum Genet, 2015. 16: p. 281-308.

Noviello, M.T., F.S.; Bondanza, A.; Tonlorenzi, R.; Rosaria Carbone, M.; Gerli, M.F.; Marktel, S.; Napolitano, S.; Cicalese, M.P.; Ciceri, F., Inflammation converts human mesoangioblasts into targets of alloreactive immune responses: Implications for allogeneic cell therapy of DMD. Mol. Ther., 2014. 22: p. 1342-1352.

Takahashi, K. and S. Yamanaka, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006. 126(4): p. 663-76.

Hashimoto A, N.A., Lee JK, Generation of Induced Pluripotent Stem Cells From Patients With Duchenne Muscular Dystrophy and Their Induction to Cardiomyocytes. Int Heart J., 2016. 57(1): p. 112-7.

Li HL, F.N.e.a., Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9. Stem Cell Reports, 2015. 4(1): p. 143-54.

Niu, X. et al. Combining single-strand oligodeoxynucleotides and CRISPR/Cas9 to correct gene mutations in Beta-thalassemia-induced Pluripotent Stem Cells. J Biol Chem, 2016.

Song, M.J. and K. Bharti, Looking into the future: Using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling. Brain Res, 2016. 1638(Pt A): p. 2-14.

K. V. Glebova, A.V.M., A. V. Baranova, M. Yu. Skoblov, Nonviral delivery systems for small interfering RNAs. Molecular Biology, 2012. 46(3): p. 349-361.

Mendell, J.R. et al. Dystrophin immunity in Duchenne’s muscular dystrophy. N Engl J Med, 2010. 363(15): p. 1429-37.

Mendell, J.R. et al. Gene therapy for muscular dystrophy: lessons learned and path forward. Neurosci Lett, 2012. 527(2): p. 90-9.

Nakamura, A., X-Linked Dilated Cardiomyopathy: A Cardiospecific Phenotype of Dystrophinopathy. Pharmaceuticals (Basel), 2015. 8(2): p. 303-20.

Tinsley, J., N. Robinson, and K.E. Davies, Safety, tolerability, and pharmacokinetics of SMT C1100, a 2-arylbenzoxazole utrophin modulator, following single- and multiple-dose administration to healthy male adult volunteers. J Clin Pharmacol, 2015. 55(6): p. 698-707.

Ricotti, V. et al. Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator, following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy. PLoS One, 2016. 11(4): p. e0152840.

Nelson, C.E. et al. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science, 2016. 351(6271): p. 403-7.

Long, C. et al. Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science, 2016. 351(6271): p. 400-3.

Jarmin, S. et al. New developments in the use of gene therapy to treat Duchenne muscular dystrophy. Expert Opin Biol Ther, 2014. 14(2): p. 209-30.

Bushby, K. et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve, 2014. 50(4): p. 477-87.

Haas, M. et al. European Medicines Agency review of ataluren for the treatment of ambulant patients aged 5 years and older with Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene. Neuromuscul Disord, 2015. 25(1): p. 5-13.

Goyenvalle, A. et al. Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science, 2004. 306(5702): p. 1796-9.

M.Yu.Skoblov, M.Yu.Skoblov. Molecular Biology, 2009. 43(6): p. 1-15.

Goemans, N.M. et al. Systemic administration of PRO051 in Duchenne’s muscular dystrophy. N Engl J Med, 2011. 364(16): p. 1513-22.

Heemskerk, H.A. et al. In vivo comparison of 2’-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping. J Gene Med, 2009. 11(3): p. 257-66.

Lu, Q.L. et al. Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc Natl Acad Sci U S A, 2005. 102(1): p. 198-203.

van Deutekom, J.C. et al. Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med, 2007. 357(26): p. 2677-86.

Yokota, T. et al. Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs. Ann Neurol, 2009. 65(6): p. 667-76.

Mendell, J.R. et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol, 2013. 74(5): p. 637-47.

Goyenvalle, A. et al. Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers. Nat Med, 2015. 21(3): p. 270-5.

Kinali, M. et al. Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol, 2009. 8(10): p. 918-28.

Lu, Q.L., S. Cirak, and T. Partridge, What Can We Learn From Clinical Trials of Exon Skipping for DMD? Mol Ther Nucleic Acids, 2014. 3: p. e152.

Veneeta Tandon, S.Y., Ashutosh Rao. FDA Efficacy Review. Available from: http://www.fda.gov/.

Sheridan, C., Duchenne muscular dystrophy drugs at the crossroads, as newer agents advance. Nat Biotechnol, 2016. 34(7): p. 675-6.

Flanigan, K.M. et al. Genetic characterization of a large, historically significant Utah kindred with facioscapulohumeral dystrophy. Neuromuscul Disord, 2001. 11(6-7): p. 525-9.

Mostacciuolo, M.L. et al. Facioscapulohumeral muscular dystrophy: epidemiological and molecular study in a north-east Italian population sample. Clin Genet, 2009. 75(6): p. 550-5.

Norwood, F.L. et al. Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. Brain, 2009. 132(Pt 11): p. 3175-86.

Padberg, G.W. et al. Facioscapulohumeral muscular dystrophy in the Dutch population. Muscle Nerve Suppl, 1995(2): p. S81-4.

Sacconi, S., L. Salviati, and C. Desnuelle, Facioscapulohumeral muscular dystrophy. Biochim Biophys Acta, 2015. 1852(4): p. 607-14.

Tawil, R. and S.M. Van Der Maarel, Facioscapulohumeral muscular dystrophy. Muscle Nerve, 2006. 34(1): p. 1-15.

M. Upadhyaya, D.N.C., G. Padberg, Facioscapulohumeral muscular dystrophy: a clinician’s experience, in: Facioscapulohumeral Muscular Dystrophy Clinical Medicine and Molecular Cell Biology. 2004: Garland Science/BIOS Scientific Publishers, Oxon, United Kingdom.

Wijmenga, C. et al. Mapping of facioscapulohumeral muscular dystrophy gene to chromosome 4q35-qter by multipoint linkage analysis and in situ hybridization. Genomics, 1991. 9(4): p. 570-5.

Deidda, G. et al. Direct detection of 4q35 rearrangements implicated in facioscapulohumeral muscular dystrophy (FSHD). J Med Genet, 1996. 33(5): p. 361-5.

de Greef, J.C. et al. Hypomethylation is restricted to the D4Z4 repeat array in phenotypic FSHD. Neurology, 2007. 69(10): p. 1018-26.

Kowaljow, V. et al. The DUX4 gene at the МЛДA locus encodes a pro-apoptotic protein. Neuromuscul Disord, 2007. 17(8): p. 611-23.

Griffin, C.A. et al. Chemokine expression and control of muscle cell migration during myogenesis. J Cell Sci, 2010. 123(Pt 18): p. 3052-60.

Tawil, R., S.M. van der Maarel, and S.J. Tapscott, Facioscapulohumeral dystrophy: the path to consensus on pathophysiology. Skelet Muscle, 2014. 4: p. 12.

Cabianca, D.S. et al. A long ncRNA links copy number variation to a polycomb/trithorax epigenetic switch in FSHD muscular dystrophy. Cell, 2012. 149(4): p. 819-31.

Gregory, G.D. et al. Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes. Mol Cell Biol, 2007. 27(24): p. 8466-79.

Tanaka, Y. et al. Trithorax-group protein ASH1 methylates histone H3 lysine 36. Gene, 2007. 397(1-2): p. 161-8.

Angela Lek, F.R., Peter L. Jones, Louis M. Kunkel, Emerging preclinical animal models for FSHD. Trends in Molecular Medicine, 2015. 21(5): p. 295-306.

van der Kooi, E.L. et al. No effect of folic acid and methionine supplementation on D4Z4 methylation in patients with facioscapulohumeral muscular dystrophy. Neuromuscul Disord, 2006. 16(11): p. 766-9.

Benson, D.W. et al. Decreased myofibrillar protein breakdown following treatment with clenbuterol. J Surg Res, 1991. 50(1): p. 1-5.

Maltin, C.A. et al. Tissue specific responses to clenbuterol; temporal changes in protein metabolism of striated muscle and visceral tissues from rats. Growth Regul, 1992. 2(4): p. 161-6.

Patel, K. and H. Amthor, The function of Myostatin and strategies of Myostatin blockade-new hope for therapies aimed at promoting growth of skeletal muscle. Neuromuscul Disord, 2005. 15(2): p. 117-26.

Wagner, K.R. et al. A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy. Ann Neurol, 2008. 63(5): p. 561-71.

Vilquin, J.T. et al. Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients. Gene Ther, 2005. 12(22): p. 1651-62.

Dib, C. et al. Correction of the FSHD myoblast differentiation defect by fusion with healthy myoblasts. J Cell Physiol, 2016. 231(1): p. 62-71.

Wallace, L.M. et al. RNA interference improves myopathic phenotypes in mice over-expressing FSHD region gene 1 (FRG1). Mol Ther, 2011. 19(11): p. 2048-54.

Himeda, C.L., T.I. Jones, and P.L. Jones, CRISPR/dCas9-mediated Transcriptional Inhibition Ameliorates the Epigenetic Dysregulation at D4Z4 and Represses DUX4-fl in FSH Muscular Dystrophy. Mol Ther, 2016. 24(3): p. 527-35.

McCullers, M.R., CRISPR-Cas9 Utilit in Genome Engineering. The Owl, 2016. 6(1): p. 62-79.

Pandey, S.N. et al. Morpholino treatment improves muscle function and pathology of Pitx1 transgenic mice. Mol Ther, 2014. 22(2): p. 390-6.

Vizoso, M. and M. Esteller, The activatory long non-coding RNA DBE-T reveals the epigenetic etiology of facioscapulohumeral muscular dystrophy. Cell Res, 2012. 22(10): p. 1413-5.

The authors declare that there are no conflicts of interest present.