COHEN VETERANS BIOSCIENCE, INC.

2024-09-18

View on USAspending

Department of Health and Human Services

DMRI-GUIDED PRE-OPERATIVE PLANNING FOR SUPRA-TOTAL RESECTION OF HIGH-GRADEGLIOMAS - ABSTRACT HIGH-GRADE GLIOMAS (HGGS) ARE THE MOST COMMON PRIMARY BRAIN MALIGNANCY IN ADULTS ASSOCIATED WITH VERY POOR SURVIVAL RATES DESPITE VARIOUS TREATMENTS. SURGERY IS THE CURRENT MAINSTAY TREATMENT FOR HGGS, AND THE MAIN FACTOR AFFECTING SURVIVAL RATES (IN OVER TWO DECADES) HAS BEEN THE INCREASED EXTENT OF RESECTION TARGETING THE “VISIBLE” CONTRAST-ENHANCING TUMOR (CET) SEEN ON CONVENTIONAL CONTRAST-ENHANCED MR IMAGING. HOWEVER, SINCE THEN RESEARCH HAS SHOWN THAT IT IS THE “INVISIBLE” NON-ENHANCING TUMOR (NET) WHICH LEADS TO PROGRESSION OR RECURRENCE IN HGGS BY INFILTRATING THE SURROUNDING WHITE MATTER (WM) TRACTS. THIS HAS LED TO THE ADOPTION OF A SUPRATOTAL RESECTION (SPTR) APPROACH, WHICH INCLUDES RESECTION OF THE `INVISIBLE' (MICROSCOPIC) CANCER BEYOND THE VISIBLE CONTRAST ENHANCED MARGINS. SPTR HAS BEEN SHOWN TO RESULT IN BETTER PATIENT OUTCOMES WITH PROGRESSION-FREE AND OVERALL SURVIVAL. SPTR IS UNDERTAKEN USING A COMBINATION OF INTRA-OPERATIVE TECHNIQUES BUT HAVING A PRE-OP ASSESSMENT OF THE FUNCTIONAL ANATOMY WILL ENHANCE THE CHANCES OF PRESERVING FUNCTION AND MAXIMIZING TUMOR RESECTION. THUS, THE OVERARCHING GOAL OF THIS ACADEMIA-INDUSTRY PARTNERSHIP (AIP) IS TO PROVIDE A TREATMENT PLANNING TOOL THAT WILL FACILITATE SAFE SPTR MAXIMIZING THE BENEFIT OF SURGICAL THERAPY WHILE PRESERVING NEUROLOGIC FUNCTION. THE PARTNERSHIP BUILDS ON THE TECHNICAL EXPERTISE OF UPENN FOR METHOD DEVELOPMENT, THE TRANSLATIONAL EXPERTISE OF SYNAPTIVE TO INTEGRATE INTO A CLINICALLY DEPLOYABLE PRODUCT, AND MOUNT SINAI'S CLINICAL EXPERTISE IN EVALUATING IT ON PATIENTS. IN AIM 1, UPENN WILL OPTIMIZE AND EVALUATE A TRACKING PARADIGM THAT PROVIDES ENHANCED VISUALIZATION OF WM FIBERS IN NET. THIS WILL ENTAIL BY COMBINING TISSUE MODELING, FIBER TRACKING AND TRACT DELINEATION IN CLINICALLY FEASIBLE MULTISHELL DMRI AND OPTIMIZE THE PARADIGM FOR REPRODUCIBILITY AND GENERALIZABILITY ACROSS PATIENTS AND ACQUISITIONS. A COMPREHENSIVE COMPARISON OF THE APPROACH TO RESEARCH AND CLINICAL PARADIGM WILL ALSO BE UNDERTAKEN USING RETROSPECTIVE DATA. THE PROTOTYPE FOR THIS TRACTOGRAPHY PARADIGM WILL BE INTEGRATED INTO THE SYNAPTIVE NEURO-NAVIGATION PRODUCT INCORPORATING CLINICAL AND REGULATORY NEEDS, WITH RIGOROUS TESTING. THE DESIGN WILL BE OPTIMIZED TO MAXIMIZE CLINICAL UTILITY ASSESSED THROUGH A MULTI-SURGEON EVALUATION ACROSS DIFFERENT SYNAPTIVE SITES. THIS WILL CULMINATE IN THE CREATION OF AN ENHANCED PLANNING TOOL. FINALLY, IN AIM 3, A PROSPECTIVE PILOT STUDY WILL BE UNDERTAKEN TO EVALUATE THIS TOOL ON CLINICAL EFFICACY FOR SAFE SPTR, WITH PATIENTS BEING LONGITUDINALLY ASSESSED FOR NEUROLOGICAL DEFICITS. AT THE END OF THIS STUDY, THE EXTENSIVE EVALUATIONS WILL POSITION THE TOOL TO A POINT OF READINESS FOR FDA SUBMISSION. THE AIP WILL LEAD TO AN ENHANCED PRE-OPERATIVE PLANNING TOOL TO PLAN SAFE SPTR, COMPLEMENTING INTRA-OPERATIVE FUNCTIONAL MAPPING, FULFILLING A CRUCIAL UNMET CLINICAL NEED. THE EXTENDED RESECTION THAT THIS TOOL WILL FACILITATE, WILL POTENTIALLY LEAD TO EXTENDED SURVIVAL TIMES AND HENCE IMPROVE PATIENT OUTCOMES. THUS, THIS TOOL IS EXPECTED TO SIGNIFICANTLY IMPACT THE CLINICAL MANAGEMENT OF BRAIN CANCER, BY AFFECTING SURGICAL TREATMENT.

627376.00

0.00

0.00

2021-07-12

View on USAspending

Department of Health and Human Services

ADDRESSING SEX AS A BIOLOGICAL VARIABLE IN PRECLINICAL PHARMACOLOGY AND NEUROSCIENCE RESEARCH: ACCOUNTING FOR NEGLECTED FACTORS AND APPLYING PRACTICAL SOLUTIONS TO ENHANCE RIGOR AND REPRODUCIBILITY - APPLICATION ID: 339139 ADDRESSING SEX AS A BIOLOGICAL VARIABLE IN PRECLINICAL PHARMACOLOGY AND NEUROSCIENCE RESEARCH: ACCOUNTING FOR NEGLECTED FACTORS AND APPLYING PRACTICAL SOLUTIONS TO ENHANCE RIGOR AND REPRODUCIBILITY ! THE NATIONAL INSTITUTES OF HEALTH (NIH) RECENTLY INSTITUTED A REQUIREMENT TO CONSIDER SEX AS A BIOLOGICAL VARIABLE IN ANIMAL STUDIES IN AN EFFORT TO ENSURE THAT PRECLINICAL RESEARCH IS APPLICABLE TO BOTH MALES AND FEMALES. THIS POLICY, HOWEVER, HAS RAISED MANY QUESTIONS ABOUT HOW RESEARCHERS SHOULD DESIGN STUDIES THAT INCLUDE BOTH MALE AND FEMALE RODENTS. ALTHOUGH SOME RESOURCES PROVIDE GUIDANCE ON THIS NEW REQUIREMENT, MOST OF THESE GUIDELINES FOCUS ON WHY SEX IS A CRITICAL BIOLOGICAL VARIABLE RATHER THAN HOW TO PRACTICALLY IMPLEMENT THESE CONSIDERATIONS INTO PRECLINICAL RESEARCH DESIGN, ANALYSES, AND REPORTING. WE PROPOSE TO DEVELOP A SERIES OF OPEN-ACCESS ONLINE TRAINING MODULES THAT PROVIDE PRECLINICAL RESEARCHERS WITH THE PRACTICAL KNOWLEDGE AND GUIDANCE THEY NEED TO CONDUCT RIGOROUS AND REPRODUCIBLE RESEARCH THAT IS APPLICABLE TO BOTH SEXES. WE AIM TO CREATE THREE MODULES, RESPECTIVELY ENTITLED “SEX DIFFERENCES AND STUDY DESIGN”, SEX DIFFERENCES IN THE BRAIN AND BEHAVIOR”, AND “SEX DIFFERENCES AND PHARMACOLOGY”. EACH MODULE WILL CONSIST OF ENGAGING SHORT VIDEOS (“EPISODES”) THAT COVER A SINGLE TOPIC IN THE FORM OF A DIDACTIC PRESENTATION AND CASE COMPARISONS. THE PRINCIPAL INVESTIGATOR AND KEY PERSONNEL WILL WORK WITH SUBJECT-MATTER EXPERTS TO DEVELOP THE MODULES. FURTHERMORE, INTERNAL EVALUATORS WILL SYSTEMATICALLY MONITOR THE PROGRAM AND PERFORM A FORMATIVE AND SUMMATIVE EVALUATION OF ITS SUCCESS ON AN ONGOING BASIS. THE EVALUATORS WILL GATHER DATA TO DETERMINE WHETHER THE PROGRAM IS MEETING ITS SPECIFIC OBJECTIVES AND GOALS AND WHETHER THE TRAINING VIDEOS ARE HELPFUL TO PRECLINICAL RESEARCHERS ACROSS ALL CAREER STAGES TO UNDERSTAND HOW TO ADDRESS SEX AS A BIOLOGICAL VARIABLE. WE WILL MAKE THESE TRAINING MODULES FREELY AVAILABLE ON YOUTUBE BY THE SECOND YEAR OF THE FUNDING PERIOD, AND POST LINKS TO THESE MODULES ACROSS THE COHEN VETERANS BIOSCIENCE, EUROPEAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY PRECLINICAL DATA FORUM NETWORK, SOCIETY FOR NEUROSCIENCE, NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES, AND JOURNAL OF NEUROSCIENCE RESEARCH, AND PARTNERSHIP FOR ASSESSMENT AND ACCREDITATION OF SCIENTIFIC PRACTICE WEBSITES. OUR GOAL IS THAT THE TRAINING MODULES WILL NOT ONLY GUIDE PRECLINICAL SCIENTISTS TO MEET THE NIH GRANT REQUIREMENT, BUT ALSO TO EMPOWER RESEARCHERS TO INCLUDE BOTH SEXES IN THEIR STUDIES. PI: PATRICIA KABITZKE INSTITUTION: COHEN VETERANS BIOSCIENCE

261347.00

0.00

0.00