Triamterene Functions as an Effective Nonsense Suppression Agent for MPS I-H (Hurler Syndrome)-Reference-Cited by-同舟云学术

Triamterene Functions as an Effective Nonsense Suppression Agent for MPS I-H (Hurler Syndrome)

Published:2023-02-24 Issue:5 Volume:24 Page:4521
ISSN:1422-0067
Container-title:International Journal of Molecular Sciences
language:en
Short-container-title:IJMS

Author:

Siddiqui Amna¹,Dundar Halil¹²^ORCID,Sharma Jyoti³⁴,Kaczmarczyk Aneta¹⁵,Echols Josh¹,Dai Yanying¹,Sun Chuanxi Richard¹,Du Ming¹³,Liu Zhong¹,Zhao Rui¹,Wood Tim⁶⁷,Sanders Shalisa⁸,Rasmussen Lynn⁸,Bostwick James Robert⁸,Augelli-Szafran Corinne⁸,Suto Mark⁸,Rowe Steven M.³^ORCID,Bedwell David M.¹³,Keeling Kim M.¹³^ORCID

Affiliation:

1. Department of Biochemistry & Molecular Genetics, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA

2. Next Generation Sequencing Transplant Diagnostics, Thermo-Fisher Scientific, West Hills, CA 91304, USA

3. Cystic Fibrosis Research Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA

4. Division of Infectious Diseases, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA

5. ARUP Laboratories, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA

6. Greenwood Genetic Center, Greenwood, SC 29646, USA

7. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA

8. Southern Research, Birmingham, AL 35205, USA

Abstract

Mucopolysaccharidosis I-Hurler (MPS I-H) is caused by the loss of α-L-iduronidase, a lysosomal enzyme that degrades glycosaminoglycans. Current therapies cannot treat many MPS I-H manifestations. In this study, triamterene, an FDA-approved, antihypertensive diuretic, was found to suppress translation termination at a nonsense mutation associated with MPS I-H. Triamterene rescued enough α-L-iduronidase function to normalize glycosaminoglycan storage in cell and animal models. This new function of triamterene operates through premature termination codon (PTC) dependent mechanisms that are unaffected by epithelial sodium channel activity, the target of triamterene’s diuretic function. Triamterene represents a potential non-invasive treatment for MPS I-H patients carrying a PTC.

Funder

Scientific and Technological Research Council of Turkey

National Institutes of Health

Cystic Fibrosis Foundation

Alabama Drug Discovery Alliance

University of Pennsylvania Orphan Disease Center

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Link

https://www.mdpi.com/1422-0067/24/5/4521/pdf

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