LXS, LLC — Department of Health and Human Services SBIR Phase II: 300

Description

Over a quarter century of research has significantly improved our understanding of the circulating cardiovascular system and its cellular componentsHoweverstudy of the parallel lymphatic system has lagged far behindlimiting our understanding of this complex and potentially clinical beneficial networkThe lymphatic system is comprised of an extensive network of vessels and nodes that parallel the venous vasculaturePeripheral lymphatic channels combine to form a single thoracic duct that enters the venous system at the confluence of the left internal jugular and subclavian veinsIt is known that the lymphatic system plays a number of roles in GI physiology including fluid homeostasisdigestionand cell mediated immunityMore recent research suggests potentially critical roles in pathophysiological conditions such as diabetescancercirrhosisand autoimmune disordersA significant obstacle in advancing lymphatic research is the ability to safely and easily collect circulating lymph and its cellular componentsThe majority of studies on circulating lymphatic cells depend on cells collected from peripheral bloodwhere lymphocytes make up less thanof circulating cellsPeripheral blood collection techniquesthe predominant type is leukapheresisare time consuming and expensiveProcessing can damage cellsaltering their genetic profile and impacting behaviorBecause of the complexity and time requiredit is difficult to obtain multiple scheduled samples and truly map changes in lymphocyte populations and non cellular components in real timeDirect sampling from the lymphatic system requires a complex open surgical cut down to locate and cannulate the thoracic duct which is not feasible for widespread clinical useparticularly in a research settingWe are proposing a novel sampling method to access and aspirate lymphocytesfluidand non cellular components directly from the thoracic ductOur approach involves a novel access catheter placed via the central venous system under ultrasound visualizationCatheterization is safe and predictableleveraging existing central venous access and guidewire techniquesAccess would provide an exponentially higher concentration of desirable cell typesThis Phase II project is divided into two Specific AimsOur preliminary studies and existing data on lymphatic anatomy and physiology suggests it will be critical in many downstream applications that our device is safe and effective over a dwell time sufficient to collect a sizable number of potentially rare cell typesreinfuse drugs or cellsor monitor the immune system during illnesstransplantationor drug administrationIn Aim I we will refine our design to facilitate longer dwell times which permit intermittentchronic aspiration and infusionDesigns will be validated first in benchtop models and later in a large animal studyIn Aim II we will undertake mechanical and biocompatibility testing required for clinical use and FDA approvalRegulatory strategy and planning are included in this approachCompletion of these activities will place the company in a position to move efficiently through regulatory approval and into clinical use Over a quarter century of research has significantly improved our understanding of the circulating cardiovascular system and its cellular componentsHoweverstudy of the parallel lymphatic system has lagged far behindlimiting our understanding of this complex and potentially clinical beneficial networkWhile it is known that the lymphatic system plays a number of roles in GI physiology and pathophysiologya significant remaining obstacle is the ability to safely and easily collect circulating lymph and its cellular componentsWe are proposing a novel transvascular access device to safely and repeatedly cannulate the thoracic ductA safe and effective method to access the lymphatic system directly would be of benefit in advancing basic and translational research in gastrointestinal medicinecatalyzing development of new clinical applications in infectious diseaseoncologyand fluid managementOnce fully realizedthis method provides an opportunity to launch a wide range of classification studies to better understand circulating lymphatic cell characteristics and dynamicsDownstream clinical applications may include selective removal of specific T cell phenotypes in GI autoimmune conditionslarge volume cell collection for ex vivo manipulationand manipulation of non cell components like exosomescholesterolchylomicronsor interstitial fluid!