Best Practices for Development and Validation of Enzymatic Activity Assays to Support Drug Development for Inborn Errors of Metabolism and Biomarker Assessment.

Autor: Azadeh M; Ultragenyx Pharmaceutical, Inc., Novato, California, USA., Good J; BioAgilytix, Durham, North Carolina, USA., Gunsior M; Astria Therapeutics, Boston, Massachusetts, USA., Kulagina N; Smithers Pharmaceutical Development Services, Gaithersburg, Maryland, USA., Lu Y; Sangamo Therapeutics, Richmond, California, USA., McNally J; BioAgilytix, Durham, North Carolina, USA., Myler H; Takeda Pharmaceuticals, Boston, Massachusetts, USA., Ni YG; Passage Bio, Inc., Philadelphia, Pennsylvania, USA., Pelto R; Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, USA., Quadrini KJ; Passage Bio, Inc., Philadelphia, Pennsylvania, USA., Vrentas C; Pharmaceutical Product Development, a ThermoFisher Company, Richmond, Virginia, USA. cevrentas@gmail.com.; Richmond, Virginia, USA. cevrentas@gmail.com., Yang L; Regenxbio, Rockville, Maryland, USA.
Jazyk: angličtina
Zdroj: The AAPS journal [AAPS J] 2024 Aug 23; Vol. 26 (5), pp. 97. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1208/s12248-024-00966-y
Abstrakt: Aberrant or dysfunctional cellular enzymes are responsible for a wide range of diseases including cancer, neurodegenerative conditions, and metabolic disorders. Deficiencies in enzyme level or biofunction may lead to intracellular accumulation of substrate to toxic levels and interfere with overall cellular function, ultimately leading to cell damage, disease, and death. Marketed therapeutic interventions for inherited monogenic enzyme deficiency disorders include enzyme replacement therapy and small molecule chaperones. Novel approaches of in vivo gene therapy and ex vivo cell therapy are under clinical evaluation and provide promising opportunities to expand the number of available disease-modifying treatments. To support the development of these different therapeutics, assays to quantify the functional activity of protein enzymes have gained importance in the diagnosis of disease, assessment of pharmacokinetics and pharmacodynamic response, and evaluation of drug efficacy. In this review, we discuss the technical aspects of enzyme activity assays in the bioanalytical context, including assay design and format as well as the unique challenges and considerations associated with assay development, validation, and life cycle management.
(© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
Databáze: MEDLINE
Externí odkaz: