Updated report on tools to measure outcomes of clinical trials in fragile X syndrome

Table 5 Potential biomarker measures in fragile X syndrome

Domains	Potential outcome Measure	Shorter term	Longer term	Quality of tools
Blood and tissue
FMR1/FMRP expression^a	FMR1 methylation	Yes	Yes	+ [9, 113, 261]
FMR1/FMRP expression^a	FMRP levels	Yes	Yes	+ [9, 113]
Signaling pathway
	ERK activation rate	Yes	Yes	+ [54, 55, 200, 203]
	BDNF level	Yes	Yes	+ [159, 204, 208]
	APP and metabolites levels	Yes	Yes	+ [159, 209]
	MMP activity	Yes	Yes	+ [87, 227]
	mTOR activity	Yes	Yes	+ [269]
	S6 Kinase activity	Yes	Yes	+ [269]
Neurophysiological
	Electroencephalogram	Yes		+[217, 218, 227, 228, 232, 233]
	Event-related potentials	Yes	Yes	+/++ [219, 222–224, 227–230]
	Prepulse inhibition (PPI)	Yes		+/++ [6, 117, 226]
	Eye tracking and pupillometry	Yes		++ [77, 85–88, 139, 216]
Neuroimaging	MRI
	sMRI	Yes	Yes	+ [235]
	-vMRI	Yes	Yes	+ [237–240]
	-DWI	Yes	Yes	+ [241–243]
	Functional MRI
	-fMRI	Yes	Yes	+ [244–250]
	-rs-fMRI	Yes	Yes	+ [77]
	-MRS	Yes	Yes	+ [270]
	-pMRI	Yes	Yes	+ [234]
	NIRS	Yes		+ [251–255]

Abbreviations: FMR1 fragile X mental retardation 1 gene, FMRP fragile X mental retardation protein, ERK extracellular signal-related kinases, BDNF brain-derived neurotrophic factor, APP amyloid precursor protein, MMP matrix metalloproteinases, mTOR mechanistic target of rapamycin, MRI magnetic resonance imaging, pMRI perfusion MRI, sMRI structural MRI, vMRI volumetric MRI, DWI diffusion-weighted imaging, fMRI functional MRI, rs-fMRI resting state fMRI, MRS magnetic resonance spectroscopy, NIRS near-infrared spectroscopy, Shorter term deemed suitable for clinical trials lasting <12 months, Longer term deemed suitable for clinical trials lasting >=12 months. Grading system: +++ strong evidence, ++ moderate evidence, + limited evidence, ? unknown due to poor methodological quality, blank cell no evidence available
^aEvaluated as a predictor of response

ISSN: 1866-1955