Table 2. Current and Experimental Remyelination Therapies Focused on Oligodendrocyte Progenitor Cell Differentiation^a.

oligodendrocyte progenitor cell (OPC) differentiation pharmacotherapies
treatment	target	method of action	discovery method	phase (clinical trial phase)
Opicinumab	LINGO-1 antagonist	antibody produced against LINGO-1	manufactured after in vitro/in vivo studies	4 ongoing phase II trials (NCT02657915,NCT01864148,NCT01721161,NCT01721161): no significant VEP latency differences
Clemastine	M1	antimuscarinic	micropillar drug screen	2 ongoing phase II trials (NCT02521311) ReBUILD: reduced VEP latencies, ReCOVER: ongoing
Benztropine	M1	antimuscarinic	small molecule drug screen	n/a
Quetiapine	M1 or H1/H3	antimuscarinic	small molecule drug screen	Ongoing I/II dose-determining study (NCT02087631)
Bexarotene	RXR agonist	nuclear translocation	in vitro/in vivo studies	n/a
IRX4204	RXR agonist	nuclear translocation	transcriptomic profiling	Recruitment phases in clinical trial for remyelination
Pioglitazone	PPARγ agonist	heterodimer w/RXR and immunomodulation	in vitro/in vivo studies	Several small-scale clinical trials completed: modest results
GW3965	LXR agonist	heterodimer w/RXR, cholesterol homeostasis	in vitro/in vivo studies	n/a
TO901317	LXR agonist	heterodimer w/RXR, cholesterol homeostasis	in vitro/in vivo studies	n/a
Clobetasol	GR/Smo agonist	glucocorticoid/Hedgehog signaling	in vitro drug screen	n/a
Miconazole	ERK1/2,CYP51	pro-growth pathways, inhibition of CYP51	in vitro drug screen	n/a

^aEach potential therapy targets varying molecular signaling components of oligodendrocyte lineage cell progression. Additionally, several therapies influence the oligodendrocyte intrinsic and extrinsic microenvironment, to facilitate OL lineage cell progression.