Small molecules as therapeutic agents for inborn errors of metabolism

• Published in: Journal of Inherited Metabolic Disease Vol. 40; no. 2; pp. 177 - 193
• Main Authors: Matalonga, Leslie, Gort, Laura, Ribes, Antonia
• Format: Journal Article Book Review
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2017; Blackwell Publishing Ltd
• Subjects: Animals; Biochemistry; Human Genetics; Humans; Infant, Newborn; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism, Inborn Errors - drug therapy; Neonatal Screening - methods; Pediatrics; Small Molecule Libraries - pharmacology; Small Molecule Libraries - therapeutic use; Ssiem 2015; Fabry Disease; Enzyme Replacement Therapy; Ambroxol; Gauche Disease; Celastrol
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-016-0005-3

Most inborn errors of metabolism (IEM) remain without effective treatment mainly due to the incapacity of conventional therapeutic approaches to target the neurological symptomatology and to ameliorate the multisystemic involvement frequently observed in these patients. However, in recent years, the therapeutic use of small molecules has emerged as a promising approach for treating this heterogeneous group of disorders. In this review, we focus on the use of therapeutically active small molecules to treat IEM, including readthrough agents, pharmacological chaperones, proteostasis regulators, substrate inhibitors, and autophagy inducers. The small molecules reviewed herein act at different cellular levels, and this knowledge provides new tools to set up innovative treatment approaches for particular IEM. We review the molecular mechanism underlying therapeutic properties of small molecules, methodologies used to screen for these compounds, and their applicability in preclinical and clinical practice.