PMID- 21253826
OWN - NLM
STAT- MEDLINE
DCOM- 20110715
LR  - 20211020
IS  - 1573-2665 (Electronic)
IS  - 0141-8955 (Linking)
VI  - 34
IP  - 2
DP  - 2011 Apr
TI  - PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X 
      nonsense mutation.
PG  - 443-7
LID - 10.1007/s10545-010-9265-5 [doi]
AB  - 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.
FAU - Tan, Lu
AU  - Tan L
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA, USA.
FAU - Narayan, Srinivas B
AU  - Narayan SB
FAU - Chen, Jie
AU  - Chen J
FAU - Meyers, Gail Ditewig
AU  - Meyers GD
FAU - Bennett, Michael J
AU  - Bennett MJ
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20110121
PL  - United States
TA  - J Inherit Metab Dis
JT  - Journal of inherited metabolic disease
JID - 7910918
RN  - 0 (Codon)
RN  - 0 (Codon, Nonsense)
RN  - 0 (Fatty Acids)
RN  - 0 (Gentamicins)
RN  - 0 (Ketones)
RN  - 0 (Oxadiazoles)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - K16AME9I3V (ataluren)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Carnitine O-Palmitoyltransferase/*genetics
MH  - Child, Preschool
MH  - Codon
MH  - *Codon, Nonsense
MH  - Fatty Acids/chemistry
MH  - Female
MH  - Fibroblasts/cytology/metabolism
MH  - Gentamicins/pharmacology
MH  - Homozygote
MH  - Humans
MH  - Hyperammonemia/genetics
MH  - Hypoglycemia/genetics
MH  - Ketones/metabolism
MH  - Liver Diseases/genetics
MH  - Mutation
MH  - Oxadiazoles/*chemistry
MH  - Oxygen/chemistry
MH  - Phenotype
MH  - Skin/metabolism
EDAT- 2011/01/22 06:00
MHDA- 2011/07/16 06:00
CRDT- 2011/01/22 06:00
PHST- 2010/02/19 00:00 [received]
PHST- 2010/12/23 00:00 [accepted]
PHST- 2010/12/13 00:00 [revised]
PHST- 2011/01/22 06:00 [entrez]
PHST- 2011/01/22 06:00 [pubmed]
PHST- 2011/07/16 06:00 [medline]
AID - 10.1007/s10545-010-9265-5 [doi]
PST - ppublish
SO  - J Inherit Metab Dis. 2011 Apr;34(2):443-7. doi: 10.1007/s10545-010-9265-5. Epub 
      2011 Jan 21.