TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - Longo, Nicola A1 - Sass, Jörn Oliver A1 - Jurecka, Agnieszka A1 - Vockley, Jerry T1 - Biomarkers for drug development in propionic and methylmalonic acidemias JF - Journal of Inherited Metabolic Disease N2 - There is an unmet need for the development and validation of biomarkers and surrogate endpoints for clinical trials in propionic acidemia (PA) and methylmalonic acidemia (MMA). This review examines the pathophysiology and clinical consequences of PA and MMA that could form the basis for potential biomarkers and surrogate endpoints. Changes in primary metabolites such as methylcitric acid (MCA), MCA:citric acid ratio, oxidation of 13C-propionate (exhaled 13CO2), and propionylcarnitine (C3) have demonstrated clinical relevance in patients with PA or MMA. Methylmalonic acid, another primary metabolite, is a potential biomarker, but only in patients with MMA. Other potential biomarkers in patients with either PA and MMA include secondary metabolites, such as ammonium, or the mitochondrial disease marker, fibroblast growth factor 21. Additional research is needed to validate these biomarkers as surrogate endpoints, and to determine whether other metabolites or markers of organ damage could also be useful biomarkers for clinical trials of investigational drug treatments in patients with PA or MMA. This review examines the evidence supporting a variety of possible biomarkers for drug development in propionic and methylmalonic acidemias. KW - biomarker KW - clinical trials KW - methylmalonic acidemia KW - pathophysiology KW - propionic acidemia KW - surrogate endpoint UN - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-60770 SN - 0141-8955 SS - 0141-8955 U6 - https://doi.org/10.1002/jimd.12478 DO - https://doi.org/10.1002/jimd.12478 PM - 35038174 VL - 45 IS - 2 SP - 132 EP - 143 PB - Wiley ER -