Table 1.

Status of Biomarker Usages in CNS Disorders

Target Disease	Compound	Sponsor Collaborator	Mechanism of Action	Pillar 1	Pillar 2	Pillar 3	Nct#	References
Schizophrenia	TAK-063	Takeda	PDE10A inhibitor		PDE10A occupancy	fMRI BOLD Ketamine-induced fMRI BOLD	NCT02370602 NCT01892189	Takano et al., 2016
Schizophrenia	PF-02545920	Pfizer	PDE10A inhibitor		PDE10A occupancy	Ketamine-induced fMRI BOLD	NCT01918202 NCT01244880
Schizophrenia	MK-0777  /TPA023	Merck & Co	GABA-Aα2/3 receptor agonist		GABA-Aα occupancy	qEEG		Atack et al., 2010 Lewis et al., 2008
Schizophrenia	bitopertin  /RG1678  /RO4917838	Roche	GlyT-1 inhibitor		GlyT-1 occupancy	CSF Glycine, Event-Related Potential	NCT01116830	Martin-Facklam et al., 2013 Hofmann et al., 2016
Schizophrenia	GSK1018921	GlaxoSmith Kline	GlyT-1 inhibitor		GlyT-1 occupancy	CSF Glycine, qEEG, mismatchnegativity	NCT00945503 NCT00527020 NCT00929370	Gunn et al., 2011
Schizophrenia	MK-2637	Merck & Co	GlyT-1 inhibitor		GlyT-1 occupancy	Motor evoked potential, qEEG	NCT00934466	Joshi et al., 2015
Schizophrenia	LY2140023 /Pomaglumetad methionil	Eli Lilly	mGlu2/3 agonist	CSF PK		Ketamine-Challenge fMRI Assay, CSF monoamine metabolites	NCT01524237	Lowe et al., 2012
Schizophrenia	JNJ-40411813	J&J	mGlu2 PAM		mGlu2 receptor occupancy 5-HT2A occupancy	Sleep EEG, Ketamine- induced psychotic symptom	NCT01359852 NCT01358006 NCT01101659 NCT01951053	Ahnaou et al., 2016
Schizophrenia	AZD8529	AstraZeneca	mGlu2 PAM	CSF PK		Ketamine-induced fMRI, EEG	NCT00985933 NCT00986531	Cook et al., 2014
Depression /FXS	RO4917523	Roche	mGlu5 antagonist		mGlu5 receptor occupancy	fMRI	NCT01483469 NCT01045083
Mild-to-moderate Alzheimer’s disease	Bapineuzumab	Janssen  /Pfizer	anti-amyloid antibody			amyloid PET, CSF p-tau, vMRI, FDG PET	NCT00575055 NCT00574132	Liu et al., 2015 Salloway et al., 2014
Mild Alzheimer’s disease	Solanezumab	Eli Lilly	anti-amyloid antibody			amyloid in blood & CSF, tau in CSF, vMRI, amyloid/tau PET, FDG PET	NCT00905372 NCT00904683 NCT01900665	Doody et al., 2014 Siemers et al., 2016
Early Alzheimer’s disease	Aducanumab  /BIIB037	Biogen	anti-amyloid antibody			amyloid PET, vMRI, FDG PET, fluid biomarkers	NCT01677572
Prodromal Alzheimer’s disease	Gantenerumab	Roche	anti-amyloid antibody			amyloid PET, amyloid and tau in CSF, vMRI, FDG PET	NCT01224106 NCT01760005
Prodromal Alzheimer’s disease	Verubecestat  /MK-8931	Merck & Co	BACE inhibitor	CSF PK		CSF Aβs & sAPPβ, amyloid PET	NCT01953601
Early Alzheimer’s disease	AZD3293	AstraZeneca  /Eli Lilly	BACE inhibitor	CSF PK		CSF Aβs & sAPPβ, amyloid PET, tau in CSF, FDG PET	NCT02245737

Abbreviatoins: Aβ, amyloid beta; BACE, beta-secretase; BOLD, blood oxygenation level dependent; CSF, cerebrospinal fluid; fMRI, functional magnetic resonance imaging; FDG, fluorodeoxyglucose; FXS, fragile X syndrome; GABA, gamma-aminobutyric acid; GlyT-1, glycine transporter 1; 5-HT, 5-hydroxytryptamine; mGlu, metabotropic glutamate; PAM, positive allosteric modulator; PDE10A, phosphodiesterase 10A; PET, positron emission tomography; PK, pharmacokinetics; qEEG, quantitative electroencephalography; sAPP, soluble amyloid precursor protein; vMRI, volumetric MRI.