Quantification of human mature frataxin protein expression in nonhuman primate hearts after gene therapy

Ian Blair, Teerapat Rojsajjakul, Juliette Hordeaux et al. Quantification of human mature frataxin protein expression in nonhuman primate hearts after gene therapy, 29 June 2023, PREPRINT (Version 1) available at Research Square doi:10.21203/rs.3.rs-3121549/v1 

Therefore, increasing expression of heart hFXN-M using gene therapy offers a way to prevent early mortality in FRDA. We used rhesus macaque monkeys to test the pharmacology of an adeno-associated virus (AAV)hu68.CB7.hFXN therapy. The advantage of using non-human primates for hFXN-M gene therapy studies is that hFXN-M and monkey FXN-M (mFXN-M) are 98.5% identical, which limits potential immunologic side-effects.

PPAR-gamma agonist pioglitazone recovers mitochondrial quality controls in fibroblasts from PITRM1-deficient patients

DArio Brunetti, A. D., Donfrancesco, C., Berlingieri, C., Frascarelli, M., Giacomello, A. P., Magalhaes Rebelo, L., Bindoff, S., Reeval, P., Filippo, M., Santorelli, G., Massaro, C. F., Viscomi, M., & Zeviani, D. (s/f). PPAR-gamma agonist pioglitazone recovers mitochondrial quality controls in fibroblasts from PITRM1-deficient patients. Front. Pharmacol. Sec. Experimental Pharmacology and Drug Discovery, 14. doi:10.3389/fphar.2023.1220620 

 We found that the pharmacological stimulation of Peroxisome Proliferator-Activated Receptor Gamma (PPARG) by Pioglitazone upregulates IDE and also PITRM1 protein levels restoring the presequence processing machinery and improving Frataxin maturation and mitochondrial function. Our findings provide mechanistic insights and suggest a potential pharmacological strategy for this rare neurodegenerative mitochondrial disease.