TABLE 1.

Summary of the existing clinical and preclinical therapeutic approaches for AHDS.

			Effects on	Effects on	Effects on	Effects on
	Treatment	Model	serum TSH	serum T4	serum T3	brain	References
TH replacement therapies	LT4	Human	↓	↑	↑	Not observed	Namba et al., 2008; Papadimitriou et al., 2008
	LT4 + T3	Human	↓	↑	↑	Not observed	Biebermann et al., 2005; Zung et al., 2011
	LT4 + PTU	Human	↓	↑	↓	Not observed	Wemeau et al., 2008; Visser et al., 2013
TH analogs treatments	DITPA	Zebrafish	N/R	N/R	N/R	Prevents hypomyelination	Zada et al., 2014, 2016
		Mouse	↓	↓	↓	Only at high doses (0.01 mg/g BW)	Di Cosmo et al., 2009; Ferrara et al., 2015
		Human	↓	↑	↓	Not observed	Verge et al., 2012
	TRIAC	Zebrafish	N/R	N/R	N/R	Prevents and rescues hypomyelination	Zada et al., 2014, 2016
		Mouse	↓	↓	↓	Only at high doses (200–400 ng/g BW) and early treatment	Kersseboom et al., 2015; Bárez-López et al., 2016
		Human	↓	↓	↓	Under Investigation	Groeneweg et al., 2019
	Sobetirome	Mice	↓	↓	↓	Modulation of TH-target genes	Bárez-López et al., 2018
Other therapies	Gene replacement therapy	Zebrafish	N/R	N/R	N/R	Rescues hypomyelination	Zada et al., 2016
		Mice	N/R	N/R	=	Modulation of TH-target genes when MCT8 is replaced at brain barriers	Iwayama et al., 2016
	Pharmacological chaperones	In vitro ex vivo	N/A	N/A	N/A	N/A	Braun and Schweizer, 2015, 2017; Groeneweg et al., 2018

↑, ↓, = : increased, decreased or not modified, respectively, versus non-treated patients or mouse model; N/R: not reported; N/A: not applicable.