Dot Laboratories, Inc. — Department of Health and Human Services SBIR Phase I: NICHD

Description

Project Summary Endometriosis is an inflammatory disorder that affects up toinwomen of reproductive agewhich is characterized by the attachment and growth of endometrial cells outside the uterus on the walls of the pelvic cavity and organsThis condition affectsof women with chronic pelvic pain and may be found in up toof infertile womenAlong with dysmenorrheapainful periodsendometriosis creates incapacitating physical symptomssuch as severe nonmenstrual painpainful sexand gastrointestinal painAsymptomatic endometriosis is a leading cause of infertilityDespite its prevalence and myriad negative impacts on quality of lifeendometriosis often goes undiagnosedOne major reason for delayed diagnosis is that no reliable noninvasive test currently existsand laparoscopic surgery is the standard procedure for confirmatory diagnosisDotLab has identified circulating microRNA biomarkers that are both sensitive and specific for endometriosisforming the basis for a non invasive test with enormous potential for transforming clinical practiceMicroRNAsmiRNAsare shortnoncoding RNA molecules that post transcriptionally regulate target genesand their altered expression has been associated with a multitude of diseasesThrough a comprehensive microarray screen of serum from women with and without endometriosisDotLab has discovered ten miRNAs that are significantly upor down regulated in endometriosis and can be readily quantified in serum and salivaIn both retrospective and prospective clinical studiescombinations of three or four of these miRNAs yielded a high diagnostic valuewith sensitivity and specificity andgtto distinguish endometriosis from other benign gynecological diseasesTwo of the main hurdles for translating the test into clinical practice aredemonstrating the generalizability of the biomarkers to identify endometriosis across diverse locationspatient populationsand stages of the diseaseanddetermining the ability of these biomarkers to indicate whether mild or severe endometriosis is presentIn Phase I we have outlined a research strategy to surmount these challengesbyvalidating the performance of our miRNA biomarkers in a multi center prospective studyin women from different geographic areas and ethnic backgroundsandconducting a pilot study to determine which of our miRNA biomarkers show the strongest correlation with two independentquantitative metrics of endometriosis severityclinicalpain symptom scoresand pathologicalbulk of diseaseSuccessful completion of this Phase I SBIR project will confirm the utility of our non invasive biomarker test and will pave the way for Phase II studies to support our in vitro diagnosticIVDregulatory submissionResults from Phase I will also be critical to help determine the sample size needed for Phase II longitudinal studies to monitor disease severity in women undergoing different endometriosis therapiesClinical use of DotLabandapos s non invasive biomarkers could dramatically improve patient care by enabling medical providers to diagnose patients soonerbegin therapy earlierand guide treatment decisions for the millions who suffer from the condition Project Narrative Overmillion women worldwide andmillion in the United States have endometriosisan estrogendependent inflammatory disorder which causes chronic pelvic paincontributes to infertilityand drastically reduces quality of lifeWe have identified a panel of circulating microRNA biomarkers for endometriosis which have great potential as a clinical tool to non invasively diagnose and monitor this diseasea significant advance form the current standard which requires surgical diagnosisIn this project we propose a multi center prospective study to confirm the high sensitivity and specificity of our biomarkers in a diverse patient population and assess their correlation with disease severity