Biomarkers for drug development in propionic and methylmalonic acidemias.

ABSTRACT: 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 ¹³ C-propionate (exhaled ¹³ CO₂ ), 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

SUBMITTER: Longo N 

PROVIDER: S-EPMC9303879 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature