Phase II: Research and Commercialization of TruT Algorithm for Free Testosterone

The measurement of testosteroneTlevels is central to the diagnosis of androgen disorderssuch as hypogonadism in men and polycystic ovary syndromePCOSin womenCirculating T is bound with high affinity to sex hormone binding globulinSHBGand with substantially lower affinity to albuminonly the free fraction is biologically activeConditions that affect SHBG concentrationssuch as aging and obesityalter total but not free T concentrationsin these conditionsthe determination of free T is necessary to obtain an accurate assessment of androgen statusTracer analog methodthe most widely used method for free Thas been shown to be inaccurateEquilibrium dialysis methodconsidered the reference methodis technically difficult to implement and standardizeand is not available in most hospital laboratoriesleading the Endocrine Society s Expert Panel to conclude thatthe calculation of free testosterone is the most useful estimate of free testosterone in plasmaThereforethere is an unmet need for algorithms that provide accurate estimates of free T that match those derived from equilibrium dialysisWe have designed a novel and accurate TruTTM algorithm for the determination of free Tbased on the characterization of testosterone s binding to SHBG using modern biophysical techniquesWe have discovered that testosterone s binding to SHBG is a dynamic multistep process that includes allosteric interaction between the two binding sites on an SHBG dimerOur computational frame work incorporates the correct binding parameters derived experimentally in these studiesthe non linear dynamics in T SHBG associationand allsoteryIn phase I studieswe demonstrated that TruTTM algorithm provides accurate free T values that match those obtained using the equilibrium dialysis in healthy and hypogoandal menWe have also shown that the binding parameters that have formed the basis of previous equationse gVermeulenare incorrectand that free T values derived using these equations deviate substantially from free T measured by equilibrium dialysisThe phase I studies have led to adoption of the TruTTM algorithm at several institutionsThe phase II program will continue the development of the TruTTM algorithm by validating it in common conditions characterized by altered SHBG concentrationssuch as obesity and agingAIMin healthy women across the menstrual cycleand in women with PCOSAimWe will generate population based reference ranges for free TAimPhase II also includes plans for commercialization of the TruTTM algorithm using a HIPAA compliant infrastructure for its clinical adoptionThe phase II program will provide validation of TruTTM algorithm in the two most common clinical indications for free T measurementmen suspected of hypogonadism and altered SHBG levelsand women with hyperandrogenic disordersIt will also enable the development of a HIPAA compliant platform that can be embedded into electronic medical record for wider clinical adoption and for improving clinical care