Huntingtonova bolest – od genskoga mapiranja do genske terapije

undergraduate thesis

• Title (english): Huntington's disease – from gene mapping to gene therapy
• Author: Jakob Šimić
• Mentor: Nenad Malenica (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-15, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Huntingtonova bolest nasljedna je neurodegenerativna bolest. Mutacija gena HTT temelji se na
povećanome broju sljedova CAG, što dovodi do povećane sklonosti agregiranju proteina
huntingtina (HTT) u živčanim stanicama mozga. Bolest se očituje u nekontroliranim pokretima,
problemima u osnovnim fizičkim aktivnostima i mentalnoj nazadnosti. U ovome radu prikazan je
pregled istraživanja Huntingtonove bolesti. Nakon što je gen HTT mapiran na četvrtome
kromosomu čovjeka i uspješno kloniran, krenuo je cijeli niz istraživanja o samoj mutaciji i njezinu
učinku na fenotip oboljele osobe na molekulskoj razini. U početku se liječenje ove bolesti svodilo
samo na ublažavanje simptoma, no pokušani su i razni molekularni pristupi liječenja poput ciljane
razgradnje mutiranoga oblika huntingtina ili utišavanja njegove ekspresije djelovanjem RNA i
specifičnim protutijelima. U najnovije vrijeme nastoji se razviti genska terapija koja bi konačno
mogla spriječiti napredovanje ove bolesti. Iako su terapije molekulama DNA, RNA i protutijelima
pokazivale određene pozitivne učinke, potencijalno najboljim lijekom doima se tominersen,
antisense specifični oligonukleotid (ASO) koji razgrađuje mutirani HTT, a još je u fazi II
kliničkoga ispitivanja.

Abstract (english)

Huntington's disease is a hereditary neurodegenerative disease. The HTT gene mutation is based
on increased CAG sequences, leading to an increased tendency to aggregate huntingtin protein
(HTT) in brain neuron cells. The disease manifests itself in uncontrolled movements, problems in
basic physical activities, and mental retardation. This paper presents an overview of Huntington's
disease research. After the HTT gene was mapped on the fourth chromosome and successfully
cloned, a whole series of research began on the mutation itself and its effect on the phenotype of
the affected person at the molecular level. In the beginning, the treatment of this disease was limited
to alleviating the symptoms, but various molecular treatment approaches were also tried, such as
the targeted degradation of the mutated form of huntingtin or the silencing of its expression by the
action of RNA or specific antibodies. Recently, efforts are being made to develop a gene therapy
that could finally prevent the progression of this disease. Although therapies with DNA and RNA
molecules and antibodies have shown some positive effects, the potentially best drug at this
moment seems to be tominersen, an antisense specific oligonucleotide (ASO) that degrades
mutated HTT, which is still in the phase II of clinical trial.

• Keywords: huntingtin; HTT; dominantno; trinukleotidi; RFLP
• Keywords (english): huntingtin; HTT; dominant; trinucleotides; RFLP
• Language: croatian
• URN:NBN: urn:nbn:hr:217:621348
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-09-18 09:45:58