Title Genska terapija u neuromuskularnim bolestima
Title (english) Gene therapy in neuromuscular diseases
Author Elena Jellin
Mentor Nina Barišić (mentor)
Committee member Mario Ćuk (predsjednik povjerenstva)
Committee member Tamara Nikuševa Martić (član povjerenstva)
Committee member Nina Barišić (član povjerenstva)
Granter University of Zagreb School of Medicine (Department of Pediatrics) Zagreb
Defense date and country 2021-07-16, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Pediatrics
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Neurology
Abstract Neuromuskularne bolesti su veoma heterogena skupina bolesti koje zahvaćaju donji motorni neuron, periferni živčani sustav, neuromuskularnu spojnicu te mišić. Neuromuskularni poremećaji su većinom genetski uvjetovani te je stoga primjena genske terapije u pedijatriji vrlo značajna. Postoji nekoliko odobrenih terapija za liječenje spinalne mišiće atrofije (SMA). Terapije poput nusinersena, protusmjernog oligonukelotida, i risdiplama, male molekule, mijenjanju mehanizam prekrajanja kako bi uključili egzon 7 u transkripte SMN2 (survival motor neuron 2) gena. Tako je dostupna povećana količina SMN (survival motor neuron) proteina i pacijenti pokazuju poboljšanu motoričku funkciju koja se ne očekuje u prirodnom tijeku bolesti. Onasemnogen abeparvovek je genska terapija s direktnom manipulacijom pacijentovog genoma. Funkcionalna kopija mutiranog gena se dostavlja putem virusnih vektora, adeno asociranih virusa (AAV). Bolesnici imaju poboljšanje motorike i razvoj novih motorički dostignuća, a povećano je i preživljenje bez korištenja trajne ventilacije. Ataluren je mala molekula koja može stabilizirati mišićnu funkciju omogućujući čitanje preranog stop kodona u pacijenata s besmislenom mutacijom uzrokovanom Duchenneovom mišićnom distrofijom (DMD). Neke terapije, primjerice, eteplirsen, ponovno uspostavljaju translacijski okvir čitanja i tako omogućuju sintezu funkcionalnog distrofina. Alglukozidaza alfa se koristi kao enzimska zamjenska terapija kod pacijenata s Pompeovom bolešću. Terapija je imala najveći učinak na poboljšanje srčane hipertrofije i preživljenje bolesnika s ranim nastupom te pokretljivost i respiratorni status u pacijenata s kasnim nastupom Pompeove bolesti. Cilj rada je prikazati genetičku podlogu određenih neuromuskularnih bolesti i njihovu odobrenu terapiju.
Abstract (english) Neuromuscular diseases are a very heterogeneous group of diseases which affect the lower motor neuron, the peripheral nervous system, the neuromuscular junction, and the muscle. Neuromuscular disorders are predominantly genetically conditioned and are therefore very important in the paediatrics. There are several approved therapies for the treatment of spinal muscular atrophy (SMA). Therapies such as nusinersen, an antisense oligonucleotide, and risdiplam, a small molecule, modify the splicing mechanism in order to include exon 7 in transcripts of the SMN2 (survival motor neuron 2) gene. Thus, an increased amount of SMN (survival motor neuron) protein is available and patients show ameliorated motor function not expected within the natural course of the disease. Onasemnogene abeparvoveck is a gene therapy which includes the direct manipulation of the patient's genome. A functional copy of the mutated gene is delivered by viral vectors - adeno associated viruses (AAV). Patients experience improvements to motor function and develop increased motor capacity, and the ventilation-free survival rate is increased as well. Ataluren is a small molecule which can stabilise the muscle function by enabling the readthrough of a premature stop codon in patients with a nonsense mutation caused Duchenne muscular dystrophy (DMD). Some therapies such as eteplirsen, re-establish a translational reading frame and therefore enable the synthesis of functional dystrophin. Alglucosidase alpha is used as an enzymatic replacement therapy for patients with Pompe disease. The therapy has demonstrated its largest impact in terms of improvement in cases of heart hypertrophy as well as survival rates in patients with infantile-onset disease, and in improving the ambulatory and respiratory status of patients with the late-onset Pompe disease. The goal of this paper is to review the genetic basis of certain neuromuscular diseases and their approved therapies.
Keywords
neuromuskularne bolesti
terapija
genska terapija
Keywords (english)
neuromuscular diseases
therapy
gene therapy
Language croatian
URN:NBN urn:nbn:hr:105:615238
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
Terms of use
Created on 2022-02-23 09:09:43