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 [Tesi di dottorato] (Unpublished)

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Item Type: Tesi di dottorato
Language: English
Title: “IDS crossing of the Blood-Brain Barrier corrects CNS defects in MPSII mice”
Creators:
CreatorsEmail
Polito, Vinicia Assuntapolito@tigem.it
Date: 27 January 2010
Number of Pages: 83
Institution: Università degli Studi di Napoli Federico II
Department: Telethon Institute of Genetics and Medicine (TIGEM)
Doctoral School: SEMM - European School of Molecular Medicine - Sede di Napoli
PHD name: Phd in Molecular Medicine (Molecular Oncology or Human Genetics)
PHD cycle: 21
PHD Coordinator:
nameemail
Salvatore, Francescosalvator@unina.it
Tutor:
nameemail
Cosma, Maria Piacosma@tigem.it
Ballabio, Andreaballabio@tigem.it
Haskins, Markmhaskins@vet.upenn.edu
Date: 27 January 2010
Number of Pages: 83
Uncontrolled Keywords: MPSII, IDS, GAG
MIUR S.S.D.: Area 06 - Scienze mediche > MED/03 - Genetica medica
Area 05 - Scienze biologiche > BIO/18 - Genetica
Area 06 - Scienze mediche > MED/04 - Patologia generale
Additional Information: Curriculum: Human Genetics
Date Deposited: 05 Feb 2010 16:14
Last Modified: 30 Apr 2014 19:41
URI: http://www.fedoa.unina.it/id/eprint/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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