Pediatric scoliosis predictive blood tests: progress and challenges for clinicians
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ORAL PRESENTATION Open Access Pediatric scoliosis predictive blood tests: progress and challenges for clinicians Alain Moreau * , Marie-Yvonne Akoume, Anita Franco, Isabelle Turgeon, Maryam Taheri, Ginette Lacroix, Ginette Larouche, BenoÎt St-Jacques, Da Shan Wang, Hubert Labelle, BenoÎt Poitras, Charles-Hilaire Rivard, Guy Grimard, Stefan Parent, Jean A Ouellet From 7th International Conference on Conservative Management of Spinal Deformities Montreal, Canada. 20-22 May 2010 Purpose There are great needs for innovative pharmacotherapies in combination with clinical tests to identify asympto- matic children at risk of developing scoliosis and symp- tomatic ones to predict who may be at risk of scoliotic curve progression. Early detection of scoliosis is critical to broaden the range of treatment options and increases effectiveness. Currently, there are no FDA cleared “pre- symptomatic” diagnostic tests available for assessing scoliosis in paediatric patients. We have developed a cell-based screening assay for the early diagnosing of presymptomatic subjects and a biochemical blood test for asymptomatic individuals and patients at different disease stage. Methods Peripheral blood samples for AIS patients, asymptomatic children and control subjects were collected in blood collection tubes containing EDTA and then centrifuged on a Ficoll-Plaque solution to obtain peripheral blood mononuclear cells (PBMCs) and plasma. Gi-coupled receptor signal transduction was measured by cellular dielectric spectroscopy (CDS) in presence of varying concentration of melatonin or other ligands. Plasma concentrations of OPN and sCD44 were measured by ELISA methods adapted to be performed on a robotic platform. Results In a cross-sectional clinical study, we have shown that mean plasma OPN levels were significantly increased in AIS patients (n=320) and correlated with disease severity with average values of 743±326 and 975±389 ng/ml for moderate and severe spinal deformities, respectively, when compared to the healthy control group (568± 216 ng/ml; n=120). Elevated plasma OPN levels were also found in the asymptomatic at-risk group (871± 387 ng/ml; n=87), suggesting that these changes precede scoliosis onset. Data obtained using PBMCs revealed a melatonin signaling impairment only in IS patients at different disease stages when compared to healthy con- trols showing a high specificity (100%) and sensitivity (100%). Risk of developing a scoliosis in asymptomatic children was determined by CDS in 33% of asympto- matic children at risk. Conclusion Both tests have a unique advantage since they can be performed without any prior knowledge of mutations in any defective genes causing AIS. The standard of care for scoliosis has not changed in any significant manner in decades. Patients today are treated in a substantially similar manner to those twenty or thirty years ago – observation, bracing, and fusion as a last resort. Our diagnostic blood-assay may have the potential to change the way scoliosis patients are diagnosed and treated. Published: 10 September 2010 doi:10.1186/1748-7161-5-S1-O3 Cite this article as: Moreau et al.: Pediatric scoliosis predictive blood tests: progress and challenges for clinicians. Scoliosis 2010 5(Suppl 1):O3. Sainte-Justine Hospital, Montreal, Canada Full list of author information is available at the end of the article Moreau et al. Scoliosis 2010, 5(Suppl 1):O3 http://www.scoliosisjournal.com/content/5/S1/O3 © 2010 Moreau et al; licensee BioMed Central Ltd.
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Transcript of Pediatric scoliosis predictive blood tests: progress and challenges for clinicians
ORAL PRESENTATION Open Access
Pediatric scoliosis predictive blood tests:progress and challenges for cliniciansAlain Moreau*, Marie-Yvonne Akoume, Anita Franco, Isabelle Turgeon, Maryam Taheri, Ginette Lacroix,Ginette Larouche, BenoÎt St-Jacques, Da Shan Wang, Hubert Labelle, BenoÎt Poitras, Charles-Hilaire Rivard,Guy Grimard, Stefan Parent, Jean A Ouellet
From 7th International Conference on Conservative Management of Spinal DeformitiesMontreal, Canada. 20-22 May 2010
PurposeThere are great needs for innovative pharmacotherapiesin combination with clinical tests to identify asympto-matic children at risk of developing scoliosis and symp-tomatic ones to predict who may be at risk of scolioticcurve progression. Early detection of scoliosis is criticalto broaden the range of treatment options and increaseseffectiveness. Currently, there are no FDA cleared “pre-symptomatic” diagnostic tests available for assessingscoliosis in paediatric patients. We have developed acell-based screening assay for the early diagnosing ofpresymptomatic subjects and a biochemical blood testfor asymptomatic individuals and patients at differentdisease stage.
MethodsPeripheral blood samples for AIS patients, asymptomaticchildren and control subjects were collected in bloodcollection tubes containing EDTA and then centrifugedon a Ficoll-Plaque solution to obtain peripheral bloodmononuclear cells (PBMCs) and plasma. Gi-coupledreceptor signal transduction was measured by cellulardielectric spectroscopy (CDS) in presence of varyingconcentration of melatonin or other ligands. Plasmaconcentrations of OPN and sCD44 were measured byELISA methods adapted to be performed on a roboticplatform.
ResultsIn a cross-sectional clinical study, we have shown thatmean plasma OPN levels were significantly increased inAIS patients (n=320) and correlated with disease severity
with average values of 743±326 and 975±389 ng/ml formoderate and severe spinal deformities, respectively,when compared to the healthy control group (568±216 ng/ml; n=120). Elevated plasma OPN levels werealso found in the asymptomatic at-risk group (871±387 ng/ml; n=87), suggesting that these changes precedescoliosis onset. Data obtained using PBMCs revealed amelatonin signaling impairment only in IS patients atdifferent disease stages when compared to healthy con-trols showing a high specificity (100%) and sensitivity(100%). Risk of developing a scoliosis in asymptomaticchildren was determined by CDS in 33% of asympto-matic children at risk.
ConclusionBoth tests have a unique advantage since they can beperformed without any prior knowledge of mutations inany defective genes causing AIS. The standard of carefor scoliosis has not changed in any significant mannerin decades. Patients today are treated in a substantiallysimilar manner to those twenty or thirty years ago –observation, bracing, and fusion as a last resort. Ourdiagnostic blood-assay may have the potential to changethe way scoliosis patients are diagnosed and treated.
Published: 10 September 2010
doi:10.1186/1748-7161-5-S1-O3Cite this article as: Moreau et al.: Pediatric scoliosis predictive bloodtests: progress and challenges for clinicians. Scoliosis 2010 5(Suppl 1):O3.
Sainte-Justine Hospital, Montreal, CanadaFull list of author information is available at the end of the article
Moreau et al. Scoliosis 2010, 5(Suppl 1):O3http://www.scoliosisjournal.com/content/5/S1/O3
© 2010 Moreau et al; licensee BioMed Central Ltd.
