TY  - JOUR
AU  - Neu, Axel
AU  - Hornig, Sönke
AU  - Sasani, Ali
AU  - Isbrandt, Dirk
AU  - Gerloff, Christian
AU  - Tsikas, Dimitris
AU  - Schwedhelm, Edzard
AU  - Choe, Chi-Un
TI  - Creatine, guanidinoacetate and homoarginine in statin-induced myopathy.
JO  - Amino acids
VL  - 52
IS  - 6-7
SN  - 1438-2199
CY  - Wien [u.a.]
PB  - Springer
M1  - DZNE-2020-01371
SP  - 1067 - 1069
PY  - 2020
AB  - Our study evaluated the effect of creatine and homoarginine in AGAT- and GAMT-deficient mice after simvastatin exposure. Balestrino and Adriano suggest that guanidinoacetate might explain the difference between AGAT- and GAMT-deficient mice in simvastatin-induced myopathy. We agree with Balestrino and Adriano that our data shows that (1) creatine possesses a protective potential to ameliorate statin-induced myopathy in humans and mice and (2) homoarginine did not reveal a beneficial effect in statin-induced myopathy. Third, we agree that guanidinoacetate can be phosphorylated and partially compensate for phosphocreatine. In our study, simvastatin-induced damage showed a trend to be less pronounced in GAMT-deficient mice compared with wildtype mice. Therefore, (phospo) guanidinoacetate cannot completely explain the milder phenotype of GAMT-deficient mice, but we agree that it might contribute to ameliorate statin-induced myopathy in GAMT-deficient mice compared with AGAT-deficient mice. Finally, we agree with Balestino and Adriano that AGAT metabolites should further be evaluated as potential treatments in statin-induced myopathy.
KW  - Amidinotransferases: deficiency
KW  - Amino Acid Metabolism, Inborn Errors
KW  - Animals
KW  - Creatine: metabolism
KW  - Creatine: pharmacology
KW  - Developmental Disabilities
KW  - Glycine: analogs & derivatives
KW  - Glycine: metabolism
KW  - Guanidinoacetate N-Methyltransferase: deficiency
KW  - Homoarginine: metabolism
KW  - Hydroxymethylglutaryl-CoA Reductase Inhibitors
KW  - Intellectual Disability
KW  - Mice
KW  - Muscular Diseases: chemically induced
KW  - Muscular Diseases: metabolism
KW  - Phosphocreatine: metabolism
KW  - Speech Disorders
LB  - PUB:(DE-HGF)16
C6  - pmid:32594255
C2  - pmc:PMC7406479
DO  - DOI:10.1007/s00726-020-02865-w
UR  - https://pub.dzne.de/record/153374
ER  -