title: Small molecules as therapeutic agents for inborn errors of metabolism.
abstract: 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.
authors.affiliation: Secció Errors Congènits del Metabolisme-IBC. Servei de Bioquímica i Genètica Molecular, Hospital Clínic, CIBERER-U737; IDIBAPS, C/ Mejía Lequerica s/n, 08028, Barcelona, Spain. lmatalonga@ciberer.es.
authors.forename: Leslie
authors.identifier: 0000-0003-0807-2570
authors.initials: L
authors.lastname: Matalonga
authors.affiliation: Secció Errors Congènits del Metabolisme-IBC. Servei de Bioquímica i Genètica Molecular, Hospital Clínic, CIBERER-U737; IDIBAPS, C/ Mejía Lequerica s/n, 08028, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Gort
authors.affiliation: Secció Errors Congènits del Metabolisme-IBC. Servei de Bioquímica i Genètica Molecular, Hospital Clínic, CIBERER-U737; IDIBAPS, C/ Mejía Lequerica s/n, 08028, Barcelona, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
mesh_terms: D000818:Animals; D006801:Humans; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000188:drug therapy*; D015997:Neonatal Screening / Q000379:methods; D054852:Small Molecule Libraries / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D054852:Small Molecule Libraries