A Phase I/II Open Label, Dose Escalation, Safety Study in Subjects With Mucopolysaccharidosis Type VI (MPS VI) Using Adeno-Associated Viral Vector 8 to Deliver the Human ARSB Gene to Liver

This study investigated the safety and efficacy of gene therapy approaches for Mucopolysaccharidosis type VI disease caused by the deficiency of arylsulfatase B (ARSB) enzyme. The aim of the study is to evaluate the safety and efficacy of the treatment.

开始日期2017-07-17

申办/合作机构

Fondazione Telethon

100 项与 AAV2/8.TBG.hARSB(Fondazione Telethon) 相关的临床结果

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100 项与 AAV2/8.TBG.hARSB(Fondazione Telethon) 相关的转化医学

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100 项与 AAV2/8.TBG.hARSB(Fondazione Telethon) 相关的专利（医药）

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项与 AAV2/8.TBG.hARSB(Fondazione Telethon) 相关的文献（医药）

2017-09-01·Molecular Therapy - Methods & Clinical Development2区 · 医学

Non-clinical Safety and Efficacy of an AAV2/8 Vector Administered Intravenously for Treatment of Mucopolysaccharidosis Type VI

2区 · 医学

ArticleOA

作者: Dell'Anno, Margherita ; Alliegro, Marialuisa ; Zuliani, Vincent ; Ferla, Rita ; Pouillot, Severine ; Nusco, Edoardo ; Auricchio, Alberto ; Galimberti, Stefania ; Marteau, Jean-Brice ; Valsecchi, Maria Grazia

In vivo gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. We recently demonstrated that AAV8-mediated liver gene transfer is effective in animal models of mucopolysaccharidosis type VI (MPS VI), a rare lysosomal storage disease that is caused by arylsulfatase B (ARSB) deficiency. In preparing for a first-in-human trial, we performed non-clinical studies to assess the safety of intravenous administrations of AAV2/8.TBG.hARSB produced under good manufacturing practice-like conditions. No toxicity was observed in AAV-treated mice, except for a transient increase in alanine aminotransferase in females and thyroid epithelial hypertrophy. AAV2/8.TBG.hARSB biodistribution and expression confirmed the liver as the main site of both infection and transduction. Shedding and breeding studies suggest that the risk of both horizontal and germline transmission is minimal. An AAV dose-response study in MPS VI mice was performed to define the range of doses to be used in the clinical study. Overall, these data support the non-clinical safety and efficacy of AAV2/8.TBG.hARSB and pave the way for a phase I/II clinical trial based on intravascular infusions of AAV8 in patients with MPS VI.

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