Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice
Mucopolysaccharidosis type I (MPS I) is the most common form of the MPS group of genetic diseases. MPS I results from a deficiency in the lysosomal enzyme α-l-iduronidase, leading to accumulation of undegraded heparan and dermatan sulphate glycosaminoglycan (GAG) chains in patient cells. MPS childre...
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doaj-0b98d3909f0341459ba9eda401fb0aea2020-11-24T22:42:42ZengMDPI AGDiseases2079-97212017-02-0151510.3390/diseases5010005diseases5010005Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I MiceAinslie L. K. Derrick-Roberts0Matilda R. Jackson1Carmen E. Pyragius2Sharon Byers3Genetics and Molecular Pathology, SA Pathology, North Adelaide, SA 5006, AustraliaGenetics and Molecular Pathology, SA Pathology, North Adelaide, SA 5006, AustraliaGenetics and Molecular Pathology, SA Pathology, North Adelaide, SA 5006, AustraliaGenetics and Molecular Pathology, SA Pathology, North Adelaide, SA 5006, AustraliaMucopolysaccharidosis type I (MPS I) is the most common form of the MPS group of genetic diseases. MPS I results from a deficiency in the lysosomal enzyme α-l-iduronidase, leading to accumulation of undegraded heparan and dermatan sulphate glycosaminoglycan (GAG) chains in patient cells. MPS children suffer from multiple organ failure and die in their teens to early twenties. In particular, MPS I children also suffer from profound mental retardation and skeletal disease that restricts growth and movement. Neither brain nor skeletal disease is adequately treated by current therapy approaches. To overcome these barriers to effective therapy we have developed and tested a treatment called substrate deprivation therapy (SDT). MPS I knockout mice were treated with weekly intravenous injections of 1 mg/kg rhodamine B for six months to assess the efficacy of SDT. Mice were assessed using biochemistry, micro-CT and a battery of behaviour tests to determine the outcome of treatment. A reduction in female bodyweight gain was observed with the treatment as well as a decrease in lung GAG. Behavioural studies showed slight improvements in inverted grid and significant improvements in learning ability for female MPS I mice treated with rhodamine B. Skeletal disease also improved with a reduction in bone mineral volume observed. Overall, rhodamine B is safe to administer to MPS I knockout mice where it had an effect on improving aspects of neurological and skeletal disease symptoms and may therefore provide a potential therapy or adjunct therapy for MPS I patients.http://www.mdpi.com/2079-9721/5/1/5mucopolysaccharidosis type Isubstrate deprivationrhodamine Blysosomal storage disorderglycosaminoglycans |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ainslie L. K. Derrick-Roberts Matilda R. Jackson Carmen E. Pyragius Sharon Byers |
spellingShingle |
Ainslie L. K. Derrick-Roberts Matilda R. Jackson Carmen E. Pyragius Sharon Byers Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice Diseases mucopolysaccharidosis type I substrate deprivation rhodamine B lysosomal storage disorder glycosaminoglycans |
author_facet |
Ainslie L. K. Derrick-Roberts Matilda R. Jackson Carmen E. Pyragius Sharon Byers |
author_sort |
Ainslie L. K. Derrick-Roberts |
title |
Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice |
title_short |
Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice |
title_full |
Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice |
title_fullStr |
Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice |
title_full_unstemmed |
Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice |
title_sort |
substrate deprivation therapy to reduce glycosaminoglycan synthesis improves aspects of neurological and skeletal pathology in mps i mice |
publisher |
MDPI AG |
series |
Diseases |
issn |
2079-9721 |
publishDate |
2017-02-01 |
description |
Mucopolysaccharidosis type I (MPS I) is the most common form of the MPS group of genetic diseases. MPS I results from a deficiency in the lysosomal enzyme α-l-iduronidase, leading to accumulation of undegraded heparan and dermatan sulphate glycosaminoglycan (GAG) chains in patient cells. MPS children suffer from multiple organ failure and die in their teens to early twenties. In particular, MPS I children also suffer from profound mental retardation and skeletal disease that restricts growth and movement. Neither brain nor skeletal disease is adequately treated by current therapy approaches. To overcome these barriers to effective therapy we have developed and tested a treatment called substrate deprivation therapy (SDT). MPS I knockout mice were treated with weekly intravenous injections of 1 mg/kg rhodamine B for six months to assess the efficacy of SDT. Mice were assessed using biochemistry, micro-CT and a battery of behaviour tests to determine the outcome of treatment. A reduction in female bodyweight gain was observed with the treatment as well as a decrease in lung GAG. Behavioural studies showed slight improvements in inverted grid and significant improvements in learning ability for female MPS I mice treated with rhodamine B. Skeletal disease also improved with a reduction in bone mineral volume observed. Overall, rhodamine B is safe to administer to MPS I knockout mice where it had an effect on improving aspects of neurological and skeletal disease symptoms and may therefore provide a potential therapy or adjunct therapy for MPS I patients. |
topic |
mucopolysaccharidosis type I substrate deprivation rhodamine B lysosomal storage disorder glycosaminoglycans |
url |
http://www.mdpi.com/2079-9721/5/1/5 |
work_keys_str_mv |
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