Transcriptional changes were found in all models, but differentially expressed genes consistent with cardiomyopathy and ISRmt were only identified in FxnG127V hearts. However, these changes were surprisingly mild even at an advanced age (18-months), despite a severe decrease in FXN levels to 1% of WT. These findings indicate that the mouse heart has low reliance on FXN, highlighting the difficulty in modeling genetically relevant FA cardiomyopathy.
Monday, September 11, 2023
Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency
Nicole M. Sayles, Jill S. Napierala, Josef Anrather, Nadège Diedhiou, Jixue Li, Marek Napierala, Hélène Puccio, Giovanni Manfredi; Comparative multi-omics analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency. Dis Model Mech 2023; dmm.050114. doi: doi:10.1242/dmm.050114
Propensity matched comparison of omaveloxolone treatment to Friedreich ataxia natural history data
Lynch, D.R., Goldsberry, A., Rummey, C., Farmer, J., Boesch, S., Delatycki, M.B., Giunti, P., Hoyle, J.C., Mariotti, C., Mathews, K.D., Nachbauer, W., Perlman, S., Subramony, S.H., Wilmot, G., Zesiewicz, T., Weissfeld, L. and Meyer, C. (2023), Propensity matched comparison of omaveloxolone treatment to Friedreich ataxia natural history data. Ann Clin Transl Neurol. doi:10.1002/acn3.51897
These results suggest a meaningful slowing of Friedreich ataxia progression with omaveloxolone, and consequently detail how propensity-matched analysis may contribute to understanding of effects of therapeutic agents. This demonstrates the direct value of natural history studies in clinical trial evaluations.
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