Cara J Westmark1. 1. Department of Neurology, University of Wisconsin-Madison, Madison, WI, USA. westmark@wisc.edu.
Abstract
BACKGROUND: Fragile X is the most common form of inherited intellectual disability and the leading known genetic cause of autism. There is currently no cure or approved medication for fragile X although various drugs target specific disease symptoms and a large number of therapeutics are in various stages of clinical development. Multiple recent clinical trials have failed on their primary endpoints indicating that there is a compelling need for validated biomarkers and outcome measures in fragile X. FINDINGS: There are currently no validated blood-based biomarkers to assess disease severity or to monitor drug efficacy in fragile X syndrome. Herein, we review candidate blood protein biomarkers including extracellular-regulated kinase, phosphoinositide 3-kinase, matrix metalloproteinase 9, amyloid-beta and amyloid-beta protein precursor. CONCLUSIONS: Bench-to-bedside plans for fragile X syndrome are severely limited by the lack of validated outcome measures. The reviewed candidate biomarkers are at early stages of validation and deserve further investigation.
BACKGROUND:Fragile X is the most common form of inherited intellectual disability and the leading known genetic cause of autism. There is currently no cure or approved medication for fragile X although various drugs target specific disease symptoms and a large number of therapeutics are in various stages of clinical development. Multiple recent clinical trials have failed on their primary endpoints indicating that there is a compelling need for validated biomarkers and outcome measures in fragile X. FINDINGS: There are currently no validated blood-based biomarkers to assess disease severity or to monitor drug efficacy in fragile X syndrome. Herein, we review candidate blood protein biomarkers including extracellular-regulated kinase, phosphoinositide 3-kinase, matrix metalloproteinase 9, amyloid-beta and amyloid-beta protein precursor. CONCLUSIONS: Bench-to-bedside plans for fragile X syndrome are severely limited by the lack of validated outcome measures. The reviewed candidate biomarkers are at early stages of validation and deserve further investigation.
Entities:
Keywords:
Amyloid beta protein precursor; Amyloid-beta; Biomarker; Extracellular-regulated kinase; Fragile X syndrome; Matrix metalloproteinase 9; Phosphoinositide 3-kinase
Authors: Paul J Lucassen; Eva F G Naninck; Johannes B van Goudoever; Carlos Fitzsimons; Marian Joels; Aniko Korosi Journal: Trends Neurosci Date: 2013-08-30 Impact factor: 13.837
Authors: Elmar W Tobi; L H Lumey; Rudolf P Talens; Dennis Kremer; Hein Putter; Aryeh D Stein; P Eline Slagboom; Bastiaan T Heijmans Journal: Hum Mol Genet Date: 2009-08-04 Impact factor: 6.150
Authors: Keith M Godfrey; Allan Sheppard; Peter D Gluckman; Karen A Lillycrop; Graham C Burdge; Cameron McLean; Joanne Rodford; Joanne L Slater-Jefferies; Emma Garratt; Sarah R Crozier; B Starling Emerald; Catharine R Gale; Hazel M Inskip; Cyrus Cooper; Mark A Hanson Journal: Diabetes Date: 2011-04-06 Impact factor: 9.461
Authors: Elmar W Tobi; P Eline Slagboom; Jenny van Dongen; Dennis Kremer; Aryeh D Stein; Hein Putter; Bastiaan T Heijmans; L H Lumey Journal: PLoS One Date: 2012-05-30 Impact factor: 3.240