Počet záznamů: 1

AAV5-MIHTT GENE THERAPY DEMONSTRATES BROAD DISTRIBUTION AND STRONG HUMAN MUTANT HUNTINGTIN LOWERING IN A HUNTINGTON DISEASE MINIPIG MODEL

SYSNO ASEP	0498974
Druh ASEP	A - Abstrakt
Zařazení RIV	O - Ostatní
Název	AAV5-MIHTT GENE THERAPY DEMONSTRATES BROAD DISTRIBUTION AND STRONG HUMAN MUTANT HUNTINGTIN LOWERING IN A HUNTINGTON DISEASE MINIPIG MODEL
Tvůrce(i)	Klíma, Jiří (UZFG-Y)_{RID, ORCID} Evers, M. (NL) Miniariková, J. (US) Juhás, Štefan (UZFG-Y)_{RID, ORCID} Vallés, A. (NL) Bohuslavová, Božena (UZFG-Y)_ORCID Juhásová, Jana (UZFG-Y)_{RID, ORCID} Kupcová Skalníková, Helena (UZFG-Y)_{RID, ORCID} Vodička, Petr (UZFG-Y)_ORCID Valeková, Ivona (UZFG-Y)_{RID, ORCID} Brouwers, C. (NL) Blits, B. (NL) Lubelski, J. (NL) Kovářová, Hana (UZFG-Y)_{RID, ORCID} van Deventer, S. (NL) Petry, H. (NL) Motlík, Jan (UZFG-Y)_{RID, ORCID} Konstantinová, P. (NL) Ellederová, Zdeňka (UZFG-Y)_{RID, ORCID}
Zdroj.dok.	Journal of Neurology Neurosurgery and Psychiatry - ISSN 0022-3050 Roč. 89, S1 (2018), A89-A89
Poč.str.	1 s.
Akce	Plenary Meeting of the European Huntington´s Disease Network (EHDN)
Datum konání	14.09.2018 - 16.09.2018
Místo konání	Vienna
Země	AT - Rakousko
Typ akce	EUR
Jazyk dok.	eng - angličtina
Země vyd.	GB - Velká Británie
Klíč. slova	AAV5-MHTT gene therapy ; Huntingtonˇs disease
Vědní obor RIV	EB - Genetika a molekulární biologie
Obor OECD	Genetics and heredity (medical genetics to be 3)
CEP	LO1609 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy
Institucionální podpora	UZFG-Y - RVO:67985904
UT WOS	000446126000241
DOI	10.1136/jnnp-2018-EHDN.240
Anotace	Background Huntington disease (HD) is a fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin gene. Great effort has been put in proof-of-concept studies of therapeutic agents in HD rodent models. One of the challenges of rodents as a model of neurodegenerative diseases is their relatively small brain, making successful translation to the HD patient difficult. This is particular relevant for gene therapy approaches, where distribution achieved upon local administration into the parenchyma is likely dependent on brain size and structure. Aims Here, we investigated the feasibility, efficacy, and tolerability of huntingtin-lowering gene therapy in a large animal brain. Methods Transgenic HD (tgHD) minipigs were injected with an engineered microRNA targeting human huntingtin, delivered via adeno-associated viral vector serotype 5 (AAV5-miHTT) or AAV5-GFP as control. The viruses were intracranially administered into the striatum and thalamus. Results We detected widespread dose-dependent distribution of AAV5-miHTT throughout the tgHD minipig brain that correlated with the engineered microRNA expression. Both human mutant huntingtin mRNA and protein were significantly reduced in all brain regions transduced by AAV5-miHTT. Conclusion The combination of widespread vector distribution and extensive huntingtin lowering observed with AAV5-miHTT supports the translation of a huntingtin-lowering gene therapy for HD from preclinical studies into the clinic.
Pracoviště	Ústav živočišné fyziologie a genetiky
Kontakt	Jana Zásmětová, knihovna@iapg.cas.cz, Tel.: 315 639 554
Rok sběru	2019

Počet záznamů: 1