Polito, Vinicia Assunta (2010) “IDS crossing of the Blood-Brain Barrier corrects CNS defects in MPSII mice”. [Tesi di dottorato] (Inedito)

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: “IDS crossing of the Blood-Brain Barrier corrects CNS defects in MPSII mice”
Autori:
AutoreEmail
Polito, Vinicia Assuntapolito@tigem.it
Data: 27 Gennaio 2010
Numero di pagine: 83
Istituzione: Università degli Studi di Napoli Federico II
Istituzioni (extra): TIGEM – Telethon Insitute of Genetics and Medicine
Dipartimento: Telethon Institute of Genetics and Medicine (TIGEM)
Scuola di dottorato: SEMM – European School of Molecular Medicine
Dottorato: PhD in Molecular Medicine (Molecular Oncology or Human Genetics)
Ciclo di dottorato: 21
Coordinatore del Corso di dottorato:
nomeemail
Salvatore, Francescosalvator@unina.it
Tutor:
nomeemail
Cosma, Maria Piacosma@tigem.it
Ballabio, Andreaballabio@tigem.it
Haskins, Markmhaskins@vet.upenn.edu
Data: 27 Gennaio 2010
Numero di pagine: 83
Parole chiave: MPSII, IDS, GAG
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/03 - Genetica medica
Area 05 - Scienze biologiche > BIO/18 - Genetica
Area 06 - Scienze mediche > MED/04 - Patologia generale
Informazioni aggiuntive: Ciclo III/XXI Curriculum Human Genetics
Depositato il: 05 Feb 2010 16:14
Ultima modifica: 12 Gen 2015 14:17
URI: http://www.fedoa.unina.it/id/eprint/4310
DOI: 10.6092/UNINA/FEDOA/4310

Abstract

IDS Crossing of the Blood-Brain Barrier Corrects CNS Defects in MPSII Mice Mucopolysaccharidosis type II (MPSII), or Hunter syndrome, arises from a deficiency in iduronate 2-sulfatase (IDS), and it is characterized by progressive somatic and neurological involvement. The MPSII mouse model reproduces the features of MPSII patients. Systemic administration of the AAV2/5CMV-hIDS vector in MPSII mouse pups results in the full correction of glycosaminoglycan (GAG) accumulation in visceral organs and in the rescue of the defects and GAG accumulation in the central nervous system (CNS). Remarkably, in treated MPSII animals, this CNS correction arises from the crossing of the blood-brain barrier by the IDS enzyme itself, not from the brain transduction. Thus, I show in this thesis that early treatment of MPSII mice with one systemic injection of AAV2/5CMV-hIDS results in prolonged and high levels of circulating IDS that can efficiently and simultaneously rescue both visceral and CNS defects for up to 18 months after therapy.

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