A Comprehensive Newborn Screening Solution for Duchenne and Congenital Muscular Dystrophies

ABSTRACT A Comprehensive Newborn Screening Solution for Duchenne and Congenital Muscular DystrophiesFast Track SBIRCongenital genetic abnormalities are a leading cause of childhood mortality and morbidityWhile routine newborn screeningNBShas dramatically improved health outcomesmany congenital disorders such as Duchenne muscular dystrophyDMDand other congenital muscular dystrophiesCMDare not currently detected by routine NBSPresymptomatic identification through NBS is critical to facilitate earlier initiation of therapies and for improved long term outcomes of patients with DMD or other CMDsWith several new therapies on the horizonthe interest in DMD screening has grown considerably and there is reason to believe testing may be adopted for public health screening in the next five yearsThe goal of this Fast Track SBIR project is to develop a complete testing solution for efficient newborn screening of DMD and CMDs from dried blood spotDBSspecimensThe system will consist of automatedlow volume biochemical assays for creatine kinaseCKenzyme activity and CK isoform expressionCK MM and CK MBfollowed bynd tier targeted next generation sequencingtNGSin CKindividuals to detect common casual gene variants associated with DMD and CMDsThe proposedst tier biochemical tests will leverage Baebiesandaposproprietary SEEKERTM platformwhich is FDA cleared for NBS of lysosomal storage disordersto provide high throughputmulti analyte CK testing to the newborn screening marketThe biochemical measurements will be combined into a decision algorithm to reduce false positives and eliminate false negativesA similar strategy is used successfully in some state NBS programs for detection of thyroid conditionswhere TSH and Tare measured simultaneously and correlated to better define disease stateThe addition of tNGS fornd tier analysis will provide further precision to our system and has the potential to revolutionize the care of infants and young children with elevated CK levelsAfter initial validation of the systemthe next steps will be to extend the clinical portion of the study to generate evidence for nomination to the Recommended Universal Screening PanelRUSPwhich states use to inform their NBS offeringsWe anticipate further validation within a Phase IIB trial concomitant with seeking CLIA certification for the screening service and eventually FDA approval of the biochemical test systemThe final product of this research will be differentiated from competing single analyte CK tests for NBS by its use of an automatedmultianalyte biochemical assayat minimal added cost compared to single analyte tests due to the tiny reagent volumes requiredand the rapidsmall sample tNGS workflowwhich combined will enable efficient identification of newborns at risk for DMD CMDs with lower false positive rates and no false negatives PROJECT NARRATIVE Congenital genetic abnormalities are a leading cause of childhood mortality and morbidityWhile routine newborn screeningNBShas dramatically improved health outcomesmany congenital disorders such as Duchenne muscular dystrophyDMDand other congenital muscular dystrophiesCMDare not currently detected by routine NBSThe goal of this Fast Track SBIR project is to develop a complete testing solution for efficient newborn screening of DMD and CMDs from dried blood spotDBSspecimensThe system will consist of automatedlow volume biochemical assays for creatine kinaseCKenzyme activity and CK isoform expressionCK MM and CK MBfollowed bynd tier targeted next generation sequencingtNGSin CKindividuals to detect common causal gene variants associated with DMD and CMDs