Generation of an induced pluripotent stem cell line (TRNDi008-A) from a Hunter syndrome patient carrying a hemizygous 208insC mutation in the  IDS  gene

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Abstract

Mucopolysaccharidosis Type II (MRS II), also known as Hunter syndrome, is a rare X-linked genetic disease caused by mutations in the IDS gene encoding iduronate 2-sulfatase (I2S). This is a multisystem disorder with significant variation in symptoms. Here, we document a human induced pluripotent stem cell (iPSC) line generated from dermal fibroblasts of a patient with Hunter syndrome containing a hemizygous mutation of a 1 bp insertion at nucleotide 208 in exon 2 of the IDS gene. The generation of this line will allow development of cell-based models for drug development, as well as the study of disease pathophysiology.

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Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy

J. Wraith, Maurizio Scarpa, Michael Beck … (2007)

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Clinical manifestations include severe airway obstruction, skeletal deformities, cardiomyopathy and, in most patients, neurological decline. Death usually occurs in the second decade of life, although some patients with less severe disease have survived into their fifth or sixth decade. Until recently, there has been no effective therapy for MPS II, and care has been palliative. Enzyme replacement therapy (ERT) with recombinant human iduronate-2-sulphatase (idursulfase), however, has now been introduced. Weekly intravenous infusions of idursulfase have been shown to improve many of the signs and symptoms and overall wellbeing in patients with MPS II. This paper provides an overview of the clinical manifestations, diagnosis and symptomatic management of patients with MPS II and provides recommendations for the use of ERT. The issue of treating very young patients and those with CNS involvement is also discussed. ERT with idursulfase has the potential to benefit many patients with MPS II, especially if started early in the course of the disease.

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A cost-effective and efficient reprogramming platform for large-scale production of integration-free human induced pluripotent stem cells in chemically defined culture

Jeanette Beers, Kaari Linask, Jane A. Chen … (2015)

Factors limiting the adoption of iPSC technology include the cost of developing lines and the time period that it takes to characterize and bank them, particularly when integration free, feeder free, and Xeno-free components are used. In this manuscript we describe our optimization procedure that enables a single technician to make 20–40 lines at a time in a 24–96 well format in a reliable and reproducible fashion. Improvements spanned the entire workflow and included using RNA virus, reducing cytotoxicity of reagents, developing improved transfection and freezing efficiencies, modifying the manual colony picking steps, enhancing passaging efficiency and developing early criteria of success. These modifications allowed us to make more than two hundred well-characterized lines per year.

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Development of idursulfase therapy for mucopolysaccharidosis type II (Hunter syndrome): the past, the present and the future

David AH Whiteman, Alan Kimura (2017)

Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM 309900) is a rare, multisystemic, progressive lysosomal storage disease caused by deficient activity of the iduronate-2-sulfatase (I2S) enzyme. Accumulation of the glycosaminoglycans dermatan sulfate and heparan sulfate results in a broad range of disease manifestations that are highly variable in presentation and severity; notably, approximately two-thirds of individuals are affected by progressive central nervous system involvement. Historically, management of this disease was palliative; however, during the 1990s, I2S was purified to homogeneity for the first time, leading to cloning of the corresponding gene and offering a means of addressing the underlying cause of MPS II using enzyme replacement therapy (ERT). Recombinant I2S (idursulfase) was produced for ERT using a human cell line and was shown to be indistinguishable from endogenous I2S. Preclinical studies utilizing the intravenous route of administration provided valuable insights that informed the design of the subsequent clinical studies. The pivotal Phase II/III clinical trial of intravenous idursulfase (Elaprase®; Shire, Lexington, MA, USA) demonstrated improvements in a range of clinical parameters; based on these findings, intravenous idursulfase was approved for use in patients with MPS II in the USA in 2006 and in Europe and Japan in 2007. Evidence gained from post-approval programs has helped to improve our knowledge and understanding of management of patients with the disease; as a result, idursulfase is now available to young pediatric patients, and in some countries patients have the option to receive their infusions at home. Although ERT with idursulfase has been shown to improve somatic signs and symptoms of MPS II, the drug does not cross the blood–brain barrier and so treatment of neurological aspects of the disease remains challenging. A number of novel approaches are being investigated, and these may help to improve the care of patients with MPS II in the future.

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Journal

Journal ID (nlm-journal-id): 101316957

Journal ID (pubmed-jr-id): 35616

Journal ID (nlm-ta): Stem Cell Res

Journal ID (iso-abbrev): Stem Cell Res

Title: Stem cell research

ISSN (Print): 1873-5061

ISSN (Electronic): 1876-7753

Publication date Nihms-submitted: 4 June 2019

Publication date (Electronic): 25 April 2019

Publication date (Print): May 2019

Publication date PMC-release: 20 July 2019

Volume: 37

Page: 101451

Affiliations

[a ]National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA

[b ]iPSC core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

[c ]Transgenic Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

Author notes

[* ]Corresponding author at: National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, MSC: 3375, Bethesda, MD 20892, USA. wzheng@ 123456mail.nih.gov (W. Zheng).

Article

Manuscript ID: NIHMS1530899

DOI: 10.1016/j.scr.2019.101451

PMC ID: 6642610

PubMed ID: 31071499

SO-VID: f44031fe-fc16-437b-b499-2cb3d48f3fd1

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This is an open access article under the CC BY license ( http://creativecommons.org/licenses/BY/4.0/).

Generation of an induced pluripotent stem cell line (TRNDi008-A) from a Hunter syndrome patient carrying a hemizygous 208insC mutation in the IDS gene

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Most cited references 5

Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy

A cost-effective and efficient reprogramming platform for large-scale production of integration-free human induced pluripotent stem cells in chemically defined culture

Development of idursulfase therapy for mucopolysaccharidosis type II (Hunter syndrome): the past, the present and the future

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