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2015 | 15 | 1 | 28-34
Article title

Rola androgenów w patogenezie i przebiegu klinicznym stwardnienia rozsianego. Nowe możliwości terapii

Content
Title variants
EN
Role of androgens in the pathogenesis and clinical course of multiple sclerosis. New therapeutic possibilities
Languages of publication
EN PL
Abstracts
EN
Multiple sclerosis is an autoimmune disease that affects the central nervous system. An autoimmune reaction directed against myelin components leads to the degradation of sheaths surrounding axons of nerve cells, thus affecting the ability of the nerves to conduct electrical impulses to and from the brain. Despite extensive studies, the aetiology and pathogenesis of this disease is still not clear. It has been shown that the interplay between genetic and environmental factors is responsible for multiple sclerosis development. The average female-to-male ratio at a typical age of disease onset is around 2.0. It means that women suffer from multiple sclerosis twice as often as men. It has also been reported that the clinical course of the disease is different in women and men. Studies showing that the female-to-male ratio is not observed in paediatric patients, suggest that sex hormones play a role in the pathogenesis of multiple sclerosis and susceptibility to this disease. Numerous studies have reported that androgens affect neural and glial cell survival in vitro. In addition, the positive effect of both endogenous and exogenous testosterone on the clinical course of multiple sclerosis in animal models has been proven. Pilot studies concerning the treatment with testosterone and selective androgen receptor modulators have shown promising tolerance and no severe side effects, suggesting that they may be good candidates for a new therapy for multiple sclerosis patients.
PL
Stwardnienie rozsiane to choroba autoimmunologiczna, która atakuje ośrodkowy układ nerwowy. Reakcja autoimmunologiczna skierowana przeciwko komponentom mieliny prowadzi do degradacji osłonki otaczającej aksony komórek nerwowych, co upośledza ich zdolność do przewodzenia impulsów – zarówno z mózgu, jak i do niego. Mimo intensywnych badań etiologia i patogeneza choroby nadal nie są dokładnie poznane. Zostało ustalone, że w rozwoju stwardnienia rozsianego biorą udział czynniki genetyczne i środowiskowe. Średni stosunek częstości występowania choroby u kobiet do częstości jej występowania u mężczyzn w przypadku typowego wieku zachorowania (między 35. a 49. rokiem życia) wynosi około 2,0, czyli kobiety zapadają na stwardnienie rozsiane dwukrotnie częściej. Także przebieg choroby i rokowanie są różne u kobiet i mężczyzn. Zależności tej nie obserwuje się wśród pacjentów pediatrycznych, co może sugerować, że hormony płciowe odgrywają istotną rolę w podatności na schorzenie i jego przebiegu. Liczne badania dowiodły istnienia wpływu androgenów na komórki nerwowe i glej in vitro. Co więcej, pozytywny wpływ zarówno testosteronu, jak i dihydrotestosteronu został udowodniony w modelach zwierzęcych stwardnienia rozsianego. Pilotażowe badania dotyczące zastosowania testosteronu i selektywnych modulatorów receptora androgenowego wykazały obiecującą tolerancję i brak poważnych efektów ubocznych, co daje nadzieję na wykorzystanie tej terapii. Krótko- i długoterminowa efektywność jej działania oraz skutki uboczne wymagają jednak dalszych badań.
Discipline
Publisher

Year
Volume
15
Issue
1
Pages
28-34
Physical description
Contributors
  • Klinika Neurologii i Udarów Mózgu, Uniwersytet Medyczny w Łodzi, Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej – Centralny Szpital Weteranów, Łódź, Polska
  • Klinika Neurologii i Udarów Mózgu, Uniwersytet Medyczny w Łodzi, Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej – Centralny Szpital Weteranów, Łódź, Polska, andrzej.glabinski@umed.lodz.pl
References
  • Ahlgren C, Odén A, Lycke J: High nationwide incidence of multiple sclerosis in Sweden. PLoS One 2014; 9: e108599.
  • Araneo BA, Dowell T, Diegel M et al.: Dihydrotestosterone exerts a depressive influence on the production of interleukin-4 (IL-4), IL-5, and gamma-interferon, but not IL-2 by activated murine T cells. Blood 1991; 78: 688–699.
  • Arias M, Dapena D, Arias-Rivas S et al.: Late onset multiple sclerosis. Neurologia 2011; 26: 291–296.
  • Banwell BL: Pediatric multiple sclerosis. Handb Clin Neurol 2013; 112: 1263–1274.
  • Banwell B, Ghezzi A, Bar-Or A et al.: Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol 2007; 6: 887–902.
  • Bebo BF, Schuster JC, Vandenbark AA et al.: Androgens alter the cytokine profile and reduce encephalitogenicity of myelin-reactive T cells. J Immunol 1999; 162: 35–40.
  • Bebo BF, Zelinka-Vincent E, Adamus G et al.: Gonadal hormones influence the immune response to PLP 139–151 and the clinical course of relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol 1998; 84: 122–130.
  • Beer S, Kesselring J: High prevalence of multiple sclerosis in Switzerland. Neuroepidemiology 1994; 13: 14–18.
  • Bhasin S, Jasuja R: Selective androgen receptor modulators as function promoting therapies. Curr Opin Clin Nutr Metab Care 2009; 12: 232–240.
  • Bove RM, Healy B, Augustine A et al.: Effect of gender on late-onset multiple sclerosis. Mult Scler 2012; 18: 1472–1479.
  • Caucheteux N, Maarouf A, Genevray M et al.: Criteria improving multiple sclerosis diagnosis at the first MRI. J Neurol 2015; 262: 979–987.
  • Chitnis T, Krupp L, Yeh A et al.: Pediatric multiple sclerosis. Neurol Clin 2011; 29: 481–505.
  • Compston A, Coles A: Multiple sclerosis. Lancet 2008; 372: 1502–1517.
  • Du C, Khalil MW, Sriram S: Administration of dehydroepiandrosterone suppresses experimental allergic encephalomyelitis in SJL/J mice. J Immunol 2001; 167: 7094–7101.
  • Eliasdottir OJ, Olafsson E, Kjartansson O: Incidence of multiple sclerosis in Iceland, 2002–2007: a population-based study. Mult Scler 2011; 17: 909–913.
  • Falaschi P, Martocchia A, Proietti A et al.: High incidence of hyperandrogenism-related clinical signs in patients with multiple sclerosis. Neuro Endocrinol Lett 2001; 22: 248–250.
  • Fromont A, Binquet C, Sauleau E et al.: National estimate of multiple sclerosis incidence in France (2001–2007). Mult Scler 2012; 18: 1108–1115.
  • Ghezzi A: Pediatric multiple sclerosis: update in diagnosis and management. Eur Neurol 2014; 72 Suppl 1: 26–28.
  • Gold SM, Chalifoux S, Giesser BS et al.: Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. J Neuroinflammation 2008; 5: 32.
  • Hussain R, Ghoumari AM, Bielecki B et al.: The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination. Brain 2013; 136: 132–146.
  • Kalincik T, Vivek V, Jokubaitis V et al.: Sex as a determinant of relapse incidence and progressive course of multiple sclerosis. Brain 2013; 136: 3609–3617.
  • Kis B, Rumberg B, Berlit P: Clinical characteristics of patients with late-onset multiple sclerosis. J Neurol 2008; 255: 697–702.
  • Koutsis G, Evangelopoulos ME, Andreadou E et al.: The onset of multiple sclerosis in Greece: a single-center study of 1,034 consecutive patients. Eur Neurol 2010; 63: 350–356.
  • Kuhle J, Disanto G, Dobson R et al.: Conversion from clinically isolated syndrome to multiple sclerosis: a large multicentre study. Mult Scler 2015; 21: 1013–1024.
  • Kuil CW, Mulder E: Effects of androgens and antiandrogens on the conformation of the androgen receptor. Ann N Y Acad Sci 1995; 761: 351–354.
  • Kułakowska A, Bartosik-Psujek H, Hożejowski R et al.: Selected aspects of the epidemiology of multiple sclerosis in Poland – a multicentre pilot study. Neurol Neurochir Pol 2010; 44: 443–452.
  • Kurtzke JF: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–1452.
  • Liguori M, Marrosu MG, Pugliatti M et al.: Age at onset in multiple sclerosis. Neurol Sci 2000; 21 Suppl 2: S825–S829.
  • Lu S, Simon NG, Wang Y et al.: Neural androgen receptor regulation: effects of androgen and antiandrogen. J Neurobiol 1999; 41: 505–512.
  • Malkki H: Multiple sclerosis: Biomarkers predict conversion from clinically isolated syndrome to multiple sclerosis. Nat Rev Neurol 2015; 11: 183.
  • Matejuk A, Hopke C, Vandenbark AA et al.: Middle-age male mice have increased severity of experimental autoimmune encephalomyelitis and are unresponsive to testosterone therapy. J Immunol 2005; 174: 2387–2395.
  • McGuigan C, McCarthy A, Quigley C et al.: Latitudinal variation in the prevalence of multiple sclerosis in Ireland, an effect of genetic diversity. J Neurol Neurosurg Psychiatry 2004; 75: 572–576.
  • Millefiorini E, Cortese A, Di Rezze S et al.: The prevalence of multiple sclerosis in central Italy. Mult Scler 2010; 16: 1432–1436.
  • Milo R, Miller A: Revised diagnostic criteria of multiple sclerosis. Autoimmun Rev 2014; 13: 518–524.
  • Modrego Pardo PJ, Latorre MA, López A et al.: Prevalence of multiple sclerosis in the province of Teruel, Spain. J Neurol 1997; 244: 182–185.
  • Moreno M, Guo F, Mills Ko E et al.: Origins and significance of astrogliosis in the multiple sclerosis model, MOG peptide EAE. J Neurol Sci 2013; 333: 55–59.
  • Otaegui D, Baranzini SE, Armañanzas R et al.: Differential micro RNA expression in PBMC from multiple sclerosis patients. PLoS One 2009; 4: e6309.
  • Palaszynski KM, Loo KK, Ashouri JF et al.: Androgens are protective in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J Neuroimmunol 2004; 146: 144–152.
  • Polman CH, Reingold SC, Banwell B et al.: Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292–302.
  • Poser CM: The epidemiology of multiple sclerosis: a general overview. Ann Neurol 1994; 36 Suppl 2: S180–S193.
  • Pugliatti M, Cossu P, Sotgiu S et al.: Clustering of multiple sclerosis, age of onset and gender in Sardinia. J Neurol Sci 2009; 286: 6–13.
  • Pugliatti M, Rosati G, Carton H et al.: The epidemiology of multiple sclerosis in Europe. Eur J Neurol 2006; 13: 700–722.
  • Robertson N, Deans J, Fraser M et al.: Multiple sclerosis in the north Cambridgeshire districts of East Anglia. J Neurol Neurosurg Psychiatry 1995; 59: 71–76.
  • Rothwell PM, Charlton D: High incidence and prevalence of multiple sclerosis in south east Scotland: evidence of a genetic predisposition. J Neurol Neurosurg Psychiatry 1998; 64: 730–735.
  • Sharpe G, Price SE, Last A et al.: Multiple sclerosis in island populations: prevalence in the Bailiwicks of Guernsey and Jersey. J Neurol Neurosurg Psychiatry 1995; 58: 22–26.
  • Sicotte NL, Giesser BS, Tandon V et al.: Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol 2007; 64: 683–688.
  • Simon JH: MRI outcomes in the diagnosis and disease course of multiple sclerosis. Handb Clin Neurol 2014; 122: 405–425.
  • Tintoré M, Arrambide G: Early onset multiple sclerosis: the role of gender. J Neurol Sci 2009; 286: 31–34.
  • Tola MA, Yugueros MI, Fernández-Buey N et al.: Prevalence of multiple sclerosis in Valladolid, northern Spain. J Neurol 1999; 246: 170–174.
  • Tremlett H, Devonshire V: Is late-onset multiple sclerosis associated with a worse outcome? Neurology 2006; 67: 954–959.
  • Tremlett H, Zhao Y, Joseph J et al.: Relapses in multiple sclerosis are age- and time-dependent. J Neurol Neurosurg Psychiatry 2008; 79: 1368–1374.
  • Tutaj M, Szczepanik M: [Mechanisms involved in the regulation of immune response in experimental autoimmune encephalomyelitis in mice]. Postepy Hig Med Dosw (Online) 2006; 60: 571–583.
  • Westerlind H, Boström I, Stawiarz L et al.: New data identify an increasing sex ratio of multiple sclerosis in Sweden. Mult Scler 2014; 20: 1578–1583.
  • Zhang WY, Hou YL: Prognostic value of magnetic resonance imaging in patients with clinically isolated syndrome conversion to multiple sclerosis: a meta-analysis. Neurol India 2013; 61: 231–238.
Document Type
review
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.psjd-5643179f-b269-4efd-b9ab-a0608b460070
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