Large animal models contribute to the development of therapies for central and peripheral nervous system dysfunction in patients with lysosomal storage diseases.

Abstract

Lysosomal storage diseases (LSDs) are a group of 70 monogenic disorders characterized by the lysosomal accumulation of a substrate. As a group, LSDs affect ~1 in 5000 live births; however, each individual storage disease is rare, limiting the ability to perform natural history studies or to perform clinical trials. Perhaps in no other biomedical field have naturally occurring large animal (canine, feline, ovine, caprine, and bovine) models been so essential for understanding the fundamentals of disease pathogenesis and for developing safe and effective therapies. These models were critical for the development of hematopoietic stem cell transplantation in α- and β- mannosidosis, fucosidosis, and the mucopolysaccharidoses; enzyme replacement therapy for fucosidosis, the mucopolysaccharidoses, and neuronal ceroid lipofuscinosis; and small molecule therapy in Niemann-Pick type C disease. However, their most notable contributions to the biomedical field are in the development of gene therapy for LSDs. Adeno-associated viral vectors to treat nervous system disease have been evaluated in the large animal models of α-mannosidosis, globoid cell leukodystrophy, GM1 and GM2 gangliosidosis, the mucopolysaccharidoses, and neuronal ceroid lipofuscinosis. This review article will summarize the large animal models available for study as well as their contributions to the development of central and peripheral nervous system dysfunction in LSDs.

• Authors: Brittney L Gurda, Charles H Vite
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 28 Issue R1 Pg. R119-R131 (10 01 2019) ISSN: 1460-2083 [Electronic] England
• PMID: 31384936 (Publication Type: Journal Article, Review)
• Copyright: © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Topics

• Animals
• Combined Modality Therapy
• Disease Management
• Disease Models, Animal
• Enzyme Replacement Therapy
• Genetic Therapy
• Hematopoietic Stem Cell Transplantation
• Humans
• Lysosomal Storage Diseases (complications, genetics)
• Nervous System Diseases (diagnosis, etiology, therapy)
• Treatment Outcome