Standardi zbrinjavanja i suvremena terapija progresivne mišićne distrofije Duchenne

master's thesis

• Title (english): Standard management and current therapies of Duchenne progressive muscular dystrophy
• Author: Tea Galić
• Mentor: Nina Barišić (mentor)
• Committee member: Irena Senečić-Čala (predsjednik povjerenstva)
• Committee member: Marija Jelušić (član povjerenstva)
• Committee member: Nina Barišić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2020-07-17, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract

Progresivna mišićna distrofija Duchenne (DMD) je X vezana progresivna mišićna bolest uzrokovana mutacijama u DMD genu zbog čega nedostaje funkcionalan protein distrofin. Duchenneova (DMD) i Beckerova (BMD) mišićna distrofija najčešće su distrofije dječje dobi. One su alelne bolesti uzrokovane mutacijom gena na istom lokusu, a razlikuju se klinički po tome što je u Beckerovoj distrofiji blaža klinička slika i bolja prognoza. Prvi klinički znakovi bolesti prezentiraju se već u dobi od 2-3 godine kao zaostajanje u motoričkom razvoju uključujući i razvoj govora, nespretnost i česte padove, a od laboratorijskih nalaza najčešće se prvo otkrivaju povišene vrijednosti jetrenih enzima kao slučajan nalaz u bolesnika sa akutnom najčešće respiratornom infekcijom. Bolest napreduje posebno do 7. godine do nepokretnosti i ovisnosti o invalidskim kolicima, potrebe za (ne)invazivnom ventilacijom do 20.-te godine te do preuranjene smrti već u drugom ili trećem desetljeću života. S obzirom na progresivnost bolesti, njeno suvremeno zbrinjavanje i terapija sveobuhvatni su i uključuju ispreplitanje medicinskih specijalnosti. Multidisciplinarni tim za zbrinjavanje DMD uključuje pedijatra, neuropedijatra, kardiologa, pulmologa, fizijatra, ortopeda, nutricionista, gastroenterologa i psihologa. Mogućnosti terapije uključuju kortikosteroide, inhibitore konvertaze angiotenzina te gensku i molekularnu terapiju, no većina je lijekova i dalje u fazama ispitivanja. Standardno zbrinjavanje uključuje terapijske postupke, lijekove i ASO. Terapija protusmjernim oligonukleotidom (ataluren/Translarna) odobrena je u Hrvatskoj i primjenjuje se kod bolesnika sa besmislenom mutacijom premature stop-codon. Provode se i daljnja istraživanja lijekova koji bi ciljali druge regije gena za potencijalno liječenje ostatka oboljele populacije. Zasad izliječenje od DMD nije moguće, no terapijom se postiže usporen napredak bolesti, poboljšava kvaliteta života oboljelih i produljuje život pacijentima.

Abstract (english)

Duchenne muscular dystrophy (DMD) is an X linked progressive muscle disease caused by mutations in DMD gene leading to a lack od functional protein dystrophin. Duchenne (DMD) and Becker (BMD) muscular dystrophies are the most common childhood dystrophies. They are allelic diseases caused by gene mutation at the same locus but what distinguishes them are milder clinical picture and better prognosis in Becker's muscular dystrophy. The first clinical signs of this disease appear around ages 2 and 3 as delayed motor skills including speech development, clumsiness and frequent falls, and elevated levels of liver enzymes are usually found in laboratory tests as a coincidental finding in patients with acute usually respiratory infection . The disease advances especially around the age of 7 to immobility and wheelchair dependency , (non)invasive ventilation necessity before the age of 20 and premature death in second or third decade of life. Regarding the progressiveness of this disease, it's contemporary care and treatment are comprehensive and include intertwining of multiple medical specialties. Multidisciplinary treatment team of DMD inculdes a pediatrician, a neuropediatrician, a cardiologist, a pulmologist, a physiatrist, an orthopedic surgeon, a gastroenterologist and a psychologist. Therapy possibilities are corticosteroids, angiotensin convertase inhibitor and gene and molecular therapy but the majority of the possible treatments is still in research phases. Standard care of DMD patients includes therapeutic procedures, drugs and ASOs. Antisense oligonucleotide therapy (ataluren/Translarna) is approved in Croatia and is applied in those patients with nonsense premature stop-codon mutation. Other drug researches are being conducted for drugs which would target other gene regions and would potentialy be used for treating the rest of the affected population. DMD is still not curable but the therapy achieves slowing of disease progresion, improves quality of life and prolongs the life of the patients.

• Keywords: mišićna distrofija; Duchenne; zbrinjavanje; terapija; ataluren
• Keywords (english): muscular dystrophy; Duchenne; care; therapy; ataluren
• Language: croatian
• URN:NBN: urn:nbn:hr:105:657801
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-09-02 08:05:42