PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation
Abstract Deficiency of carnitine palmitoyltransferase 1A (CPT1A) results in impaired hepatic long‐chain fatty acid oxidation and ketogenesis. We have previously described a patient with a severe CPT1A phenotype who is homozygous for the nonsense mutation 478 C > T (R160X). It has been known for s...
Published in: | Journal of Inherited Metabolic Disease |
---|---|
Main Authors: | , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Wiley
2011
|
Subjects: | |
Online Access: | http://dx.doi.org/10.1007/s10545-010-9265-5 https://onlinelibrary.wiley.com/doi/pdf/10.1007/s10545-010-9265-5 https://onlinelibrary.wiley.com/doi/full-xml/10.1007/s10545-010-9265-5 |
id |
crwiley:10.1007/s10545-010-9265-5 |
---|---|
record_format |
openpolar |
spelling |
crwiley:10.1007/s10545-010-9265-5 2024-06-23T07:54:12+00:00 PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation Tan, Lu Narayan, Srinivas B. Chen, Jie Meyers, Gail Ditewig Bennett, Michael J. 2011 http://dx.doi.org/10.1007/s10545-010-9265-5 https://onlinelibrary.wiley.com/doi/pdf/10.1007/s10545-010-9265-5 https://onlinelibrary.wiley.com/doi/full-xml/10.1007/s10545-010-9265-5 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Journal of Inherited Metabolic Disease volume 34, issue 2, page 443-447 ISSN 0141-8955 1573-2665 journal-article 2011 crwiley https://doi.org/10.1007/s10545-010-9265-5 2024-06-06T04:24:13Z Abstract Deficiency of carnitine palmitoyltransferase 1A (CPT1A) results in impaired hepatic long‐chain fatty acid oxidation and ketogenesis. We have previously described a patient with a severe CPT1A phenotype who is homozygous for the nonsense mutation 478 C > T (R160X). It has been known for some time that gentamicin can promote readthrough of nonsense codons. Recently, a new compound (PTC124) with less clinical toxicity than gentamicin has been indicated as a therapy for patients with nonsense mutations for multiple genetic diseases. The study is designed to investigate whether PTC124 can promote readthrough of the R160X CPT1A mutation and increase normal sized CPT1 protein expression and activity in the patient's skin fibroblasts. Our study demonstrated that after both PTC 124 and gentamicin treatment, there was an increase in CPT1 activity in patient fibroblasts to levels that are similar to that of the mild Inuit P479L variant. Our results provide additional evidence for proof of principle that PTC124 is a potential therapeutic agent for treating patients with any genetic condition that results from a nonsense mutation. Article in Journal/Newspaper inuit Wiley Online Library Journal of Inherited Metabolic Disease 34 2 443 447 |
institution |
Open Polar |
collection |
Wiley Online Library |
op_collection_id |
crwiley |
language |
English |
description |
Abstract Deficiency of carnitine palmitoyltransferase 1A (CPT1A) results in impaired hepatic long‐chain fatty acid oxidation and ketogenesis. We have previously described a patient with a severe CPT1A phenotype who is homozygous for the nonsense mutation 478 C > T (R160X). It has been known for some time that gentamicin can promote readthrough of nonsense codons. Recently, a new compound (PTC124) with less clinical toxicity than gentamicin has been indicated as a therapy for patients with nonsense mutations for multiple genetic diseases. The study is designed to investigate whether PTC124 can promote readthrough of the R160X CPT1A mutation and increase normal sized CPT1 protein expression and activity in the patient's skin fibroblasts. Our study demonstrated that after both PTC 124 and gentamicin treatment, there was an increase in CPT1 activity in patient fibroblasts to levels that are similar to that of the mild Inuit P479L variant. Our results provide additional evidence for proof of principle that PTC124 is a potential therapeutic agent for treating patients with any genetic condition that results from a nonsense mutation. |
format |
Article in Journal/Newspaper |
author |
Tan, Lu Narayan, Srinivas B. Chen, Jie Meyers, Gail Ditewig Bennett, Michael J. |
spellingShingle |
Tan, Lu Narayan, Srinivas B. Chen, Jie Meyers, Gail Ditewig Bennett, Michael J. PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation |
author_facet |
Tan, Lu Narayan, Srinivas B. Chen, Jie Meyers, Gail Ditewig Bennett, Michael J. |
author_sort |
Tan, Lu |
title |
PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation |
title_short |
PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation |
title_full |
PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation |
title_fullStr |
PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation |
title_full_unstemmed |
PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation |
title_sort |
ptc124 improves readthrough and increases enzymatic activity of the cpt1a r160x nonsense mutation |
publisher |
Wiley |
publishDate |
2011 |
url |
http://dx.doi.org/10.1007/s10545-010-9265-5 https://onlinelibrary.wiley.com/doi/pdf/10.1007/s10545-010-9265-5 https://onlinelibrary.wiley.com/doi/full-xml/10.1007/s10545-010-9265-5 |
genre |
inuit |
genre_facet |
inuit |
op_source |
Journal of Inherited Metabolic Disease volume 34, issue 2, page 443-447 ISSN 0141-8955 1573-2665 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1007/s10545-010-9265-5 |
container_title |
Journal of Inherited Metabolic Disease |
container_volume |
34 |
container_issue |
2 |
container_start_page |
443 |
op_container_end_page |
447 |
_version_ |
1802646247965720576 |