Title Uloga IFN-β u patogenezi i liječenju multiple skleroze
Title (english) The role of IFN-β in the pathogenesis and therapy of multiple sclerosis
Author Karlo Mladenić
Mentor Ivana Munitić (mentor)
Committee member Hrvoje Jakovac (predsjednik povjerenstva)
Committee member Rozi Andretić Waldowski (član povjerenstva)
Committee member Ivana Munitić (član povjerenstva)
Granter University of Rijeka (Faculty of Biotechnology and Drug Development) Rijeka
Defense date and country 2018-09-13, Croatia
Scientific / art field, discipline and subdiscipline BIOTECHNICAL SCIENCES Biotechnology
Abstract Multipla skleroza (MS) je kronična autoimuna bolest koja napada mijelinizirane aksone u središnjem živčanom sustavu (SŽS-u). Posljedica autoimunog napada je demijelinizacija koja dovodi do gubitka neuronske signalizacije, a ponekad i do smrti neurona. MS se može očitovati različitim simptomima poput senzoričkih, vizualnih i motoričkih poremećaja, umora, boli i kognitivnih deficita, a njihova manifestacija varira od pacijenta do pacijenta. Točan uzrok nastanka MS-a nije poznat, no niz genetskih i okolišnih faktora može doprinijeti njenoj patogenezi pa se bolest smatra multifaktorijalnom. Javlja se u dobi od 20-40 godina, a pogađa 2,5 milijuna ljudi širom svijeta. Postoje 4 tipa MS-a: relapsno remitirajući, sekundarno progresivni, primarno progresivni i progresivno relapsni. Terapije za MS smanjuju trajanje akutnih napada bolesti, njihovu frekvenciju i ublažavaju simptome, ali nažalost, ne liječe MS. Budući da imunološki sustav igra centralnu ulogu u patogenezi bolesti, sve trenutno dostupne terapije su imunomodulacijske. Uloga imunološkog sustava u patogenezi bolesti je detaljno objašnjena u ovom radu. Napravljen je i iscrpan pregled mehanizama djelovanja i učinkovitosti terapije imunomodulacijskim citokinom IFN-β, prvom terapijom za MS. IFN-β smanjuje godišnju stopu pojave napada te smanjuje aktivnost i napredovanje bolesti, ali s vremenom gubi kliničku učinkovitost. U ovom radu je obrađen učinak IFN-β na transport imunoloških stanica do SŽS-a, aktivnost B stanica, antigen prezentirajućih stanica i T stanica te njegovo direktno neuroprotektivno djelovanje. Unatoč njegovom pleiotropnom učinku na imunološki sustav, IFN-β ne liječi MS, a kao glavni razlog neuspjeha smatra se pojava neutralizirajućih protutijela koja se razvijaju u velikom broju pacijenata tijekom liječenja s IFN-β. Terapija IFN-β je napredovala s novom formulacijom pegiliranog IFN-β koja ima veću kliničku učinkovitost. Još uvijek ima prostora za poboljšanje terapije IFN-β, a potencijalni načini su predloženi u ovom radu.
Abstract (english) Multiple sclerosis is a chronic autoimmune disorder that targets myelinated axons in the central nervous system (CNS). This results in demyelinization which leads to loss of neuronal signalization and sometimes even to neuronal death. MS is characterized by various symptoms such as sensory, visual and motor disorders, fatigue, pain and cognitive deficits. Their manifestation varies from patient to patient. MS is a multifactorial disease that can be influenced by various genetic and environmental factors, but the exact cause is still unknown. It occurs at the age of 20-40 and affects 2,5 million people worldwide. There are 4 types of MS: relapsing remitting, secondary progressive, primary progressive and progressive relapsing. MS therapies reduce the duration of acute exacerbations, their frequency and relieve symptoms, but unfortunately, they are unable to cure the disease. Since the immune system plays a central role in disease pathogenesis, all currently available therapies are immunomodulatory. The role of the immune system in pathogenesis of the disease is described in detail in this work. This work also contain an extensive overview of the mechanisms of action and efficacy of immunomodulatory cytokine IFN-β, the first MS therapy. IFN-β treatment reduces the annual relapse rate, reduces activity and progression of the disease, but generally does not have long-term effect because its clinical efficacy is decreasing over time. This work explains effects of IFN-β on transport of immune cells to the CNS, B cell activity, antigen presenting cells, T cell activity and its direct neuroprotective functions. Despite its pleiotropic effect on the immune system, IFN-β does not cure MS and neutralizing antibodies that develop in a large number of patients treated with IFN-β have been proposed as the main cause of treatment failure. IFN-β therapy has progressed with the new formulation of pegylated IFN-β that has greater clinical efficacy. There
is still room for improvement of IFN-β therapy and potential ways are discussed in this work.
Keywords
Multipla skleroza
autoimune bolesti
demijelinizacija
imunomodulatorne terapije
IFN-β
Keywords (english)
Multiple sclerosis
autoimmune diseases
demyelinization
immunomodulatory therapies
IFN-β
Language croatian
URN:NBN urn:nbn:hr:193:727115
Study programme Title: Biotechnology and drug research Study programme type: university Study level: undergraduate Academic / professional title: sveučilišni/a prvostupnik/prvostupnica biotehnologije i istraživanja lijekova (sveučilišni/a prvostupnik/prvostupnica biotehnologije i istraživanja lijekova)
Type of resource Text
File origin Born digital
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Created on 2018-11-06 07:32:33