Long non-coding RNA signatures to classify multiple sclerosis

Diagnosis of relapsing remitting multiple sclerosisMSrests on clinical symptoms and examinations asoutlined in the revised McDonald s criteria supported by appropriate magnetic resonance imaging findings andother laboratory testsThe need for early diagnosis is clearly emphasized in a position paper produced inby MS Brain Health organization calledBrain healthTime matters in multiple sclerosiswhich is endorsed bythe major organizations and foundations that advocate for MS researchproviders and patients includingAccelerated Cure ProjectACPAmericans Committed for Treatment and Research in Multiple SclerosisACTRIMSThe Consortium of Multiple Sclerosis CentersCMSCEuropean Brain CouncilEBCEuropeanCommittee for Treatment and Research in Multiple SclerosisECTRIMSEuropean Multiple Sclerosis PlatformEMSPInternational Society of NeuroimmunologyISNIInternational Organization of Multiple SclerosisNursesIOMSNNational Multiple Sclerosis SocietyNMSSand Multiple Sclerosis TrustMSTo cite fromtheir executive summary pageA therapeutic strategy that offers the best chance of preserving brainand spinal cord tissue early in the disease course needs to be widely acceptedand urgently adoptedSignificant delays often occur before a person with symptoms suggestive of MS sees a neurologistfor diagnosis and treatmentEarly intervention is vitalbold type face is theirsnot oursThe question of whether or not disease classifiers capable of providing clinically useful information could bebuilt based upon disease specific expression levels of mRNAs in whole blood has been a subject of research forseveral yearsLong non coding RNAslncRNAare recently discovered regulatory RNA molecules that do notcode for proteins but influence a vast array of biological processesIt is also thought that lncRNAs drive biologiccomplexity observed in vertebrates that may also be reflected by the greater array of complex idiopathic diseasesthat humans developAs suchour data obtained in the phaseportion of this worksupport the notion thatdisease associated lncRNAs exhibit far greater differences in expression than disease associated mRNAsInthis applicationwe propose to explore the hypothesis that lncRNAs are better biomarkers of human diseasethan mRNAsHerewe will focus on MS as a disease category and have identified and validated MS associateddifferentially expressed lncRNAsStudy of lncRNAs in human autoimmune disease is in its infancy andexploration of lncRNAs as biomarkers of autoimmune disease has not been previously addressedWe proposeto determine expression levels of target lncRNAs in blood obtained from larger cohorts of subjects that includesubjects with RRMShealthy controlsneurologic disease controls including both inflammatory and noninflammatory disordersandperipheral autoimmune disease controls obtained from various sites in the U Sand Europe to establish a wide geographic distribution and to identify optimum machine learning classifiers todistinguish the MS cohorts from healthy and disease control cohorts with greatest overall accuracy