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  -