SBIR-STTR Award

PharmacoPhotonics, LLC proposes research leading to a novel 2-photon in vivo fluorescence method for monitoring glomerular filtration rate (GFR) in acute kidney injury (AKI). AKI remains a vexing clinical problem resulting in unacceptably high patient mortality, development of chronic kidney disease and enhanced progression to end stage renal disease. Although clinical risks factors for developing AKI have been identified, we have no reasonable surveillance technique ("biomarker") to definitively and rapidly diagnose or determine the extent of severity of AKI in any patient. Since patient outcomes correlate with the extent of injury, and effective therapy requires early intervention, the ability to rapidly diagnose and stratify patients by their level of kidney injury is paramount for clinical progress in this field. Therefore, we are developing and characterizing an optical measurement technique that can rapidly, accurately and repetitively quantify the glomerular filtration rate (GFR) independent of serum or urinary measurements. It is our intention to more thoroughly characterize this approach using multi-photon microscopy and our patented ratiometric technique utilizing two fluorescent reporter molecules. This quantitative ratiometric optical approach minimizes the inherent limitations of intensity fluorescence determinations and allows for rapid and accurate determination of GFR. The purpose of this Phase 1 STTR project is to identify the best molecular candidate, both in composition and molecular size, to be used for quantifying GFR and at the same time minimizing non-renal clearance of candidate molecules. We will then extend these observations into animal models of acute kidney injury including ischemia, sepsis, and nephrotoxins such as aminoglycosides and radiocontrast agents. These studies will set the foundation for development of our noninvasive optical detection apparatus in a Phase 2 application. PUBLIC HEALTH RELEVANCE Acute kidney injury remains a major health care burden with a high mortality rate. At the present time there is no diagnostic test for rapid detection or determination of the severity of injury. This has limited the ability to effectively test potential new therapies. PharmacoPhotonics, LLC is developing a non-invasive optical technique to meet this need.

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PharmacoPhotonics (FAST Diagnostics), LLC proposes research to extend the Phase I STTR leading to a novel 2-photon in vivo fluorescence method for monitoring glomerular filtration rate (GFR) in acute kidney injury (AKI). AKI remains a vexing clinical problem resulting in unacceptably high patient mortality, development of chronic kidney disease and enhanced progression to end stage renal disease. Although clinical risks factors for developing AKI have been identified, there is no reasonable surveillance technique (""biomarker"") to definitively and rapidly diagnose or determine the extent of severity of AKI in any patient. Since patient outcomes correlate with the extent of injury, and effective therapy requires early intervention, the ability to rapidly diagnose and stratify patients by their level of kidney injury is paramount for clinical progress in this field. Therefore, FAST is developing and characterizing an optical measurement technique utilizing a novel minimally invasive Ratiometric Fluorescence Device (RFD) that can rapidly, accurately, and repetitively quantify the GFR, independent of serum or urinary measurements. FAST intends to more thoroughly characterize this approach using multi-photon microscopy and their patented ratiometric technique utilizing two fluorescent reporter molecules. This quantitative ratiometric optical approach minimizes the inherent limitations of intensity fluorescence determinations and allows for rapid and accurate determination of GFR. FAST will also initiate the development of a noninvasive device and marker molecules. Therefore, the purpose of this Phase II STTR project is to characterize the RFD in rats and then dogs, both under physiologic and AKI conditions, utilizing data on molecular markers gained in the Phase I study. FAST will then extend these observations into animal models of AKI including ischemia, sepsis, and nephrotoxins, such as aminoglycosides and radiocontrast agents. These studies will set the foundation for use of the RFD in human studies and further development of an initial noninvasive optical detection apparatus.

Public Health Relevance:
Acute Kidney Injury (AKI) is a major and rapidly increasing cause of morbidity and mortality in hospitalized patients. Unfortunately, there is at present no diagnostic method to either rapidly diagnose and or quantify the extent of AKI, both of which are known to be important in the prognosis and treatment. FAST Diagnostics has developed a ratiometric fluorescent device and an associated technique allowing for rapid quantification of kidney function during AKI.

Thesaurus Terms:
1,3-Benzenedicarboxamide, 5-(Acetyl(2,3-Dihydroxypropyl)Amino)-N,N'-Bis(2,3-Dihydroxypropyl)-2,4,6-Triiodo-; 4h-Imidazol-4-One, 2-Amino-1,5-Dihydro-1-Methyl-; Acute; Acute Renal Failure With Renal Papillary Necrosis; Aged 65 And Over; Aminoglycosides; Animal Model; Animal Models And Related Studies; Blood; Blood Plasma; Blood Serum; Blood Vessels; Crea; Canine Species; Canis Familiaris; Cardiac; Catheters; Causality; Cell Communication And Signaling; Cell Signaling; Chronic; Chronic Kidney Failure; Chronic Renal Disease; Clinical; Clinical Trials, Phase I; Common Rat Strains; Creatinine; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Method; Diagnostic Procedure; Diagnostic Technique; Disease Model; Dogs; Esrd; Early Diagnosis; Early Treatment; Early-Stage Clinical Trials; Elderly; Elderly, Over 65; End Stage Renal Failure; End-Stage Kidney Disease; Equation; Equilibrium; Etiology; Fiber Optics; Fluorescence; Forecast Of Outcome; Foundations; Future; Glomerular Filtration Rate; Hepatic Disorder; Hour; Human; Human, General; Image; Indiana; Injury; Intracellular Communication And Signaling; Inulin; Iohexol; Iohexol 350; Ischemia; Kidney; Kidney Failure, Chronic; Label; Legal Patent; Licensing; Liver Diseases; Maintenance; Maintenances; Mammals, Dogs; Mammals, Rats; Man (Taxonomy); Man, Modern; Measurement; Measures; Method Loinc Axis 6; Methodology; Methods; Methods And Techniques; Methods, Other; Microscopic; Microscopy; Modeling; Monitor; Morbidity; Morbidity - Disease Rate; Mortality; Mortality Vital Statistics; Optics; Outcome; Patents; Patient Care; Patient Care Delivery; Patients; Phase; Phase 1 Clinical Trials; Phase I Clinical Trials; Phase I Study; Photons; Physiologic; Physiological; Plasma; Procedures; Prognosis; Radioactivity; Rat; Rattus; Recovery; Renal Disease, End-Stage; Renal Failure, Chronic; Renal Function; Reporter; Research; Reticuloendothelial System, Blood; Reticuloendothelial System, Serum, Plasma; Risk Factors; Sttr; Sepsis; Serum; Serum, Plasma; Severities; Signal Transduction; Signal Transduction Systems; Signaling; Small Business Technology Transfer Research; Standardization; Stream; System; System, Loinc Axis 4; Techniques; Technology; Testing; Time; Universities; Urinary System, Kidney; Acute Kidney Injury; Advanced Age; Balance; Balance Function; Base; Biological Signal Transduction; Biomarker; Bloodstream Infection; Canine; Chronic Kidney Disease; Detector; Diabetic; Disease Causation; Disease Etiology; Disease/Disorder Etiology; Disorder Etiology; Disorder Model; Domestic Dog; Early Detection; Effective Therapy; Elders; Geriatric; Hepatopathy; High Risk; Imaging; Improved; In Vivo; Kidney Function; Late Life; Later Life; Liver Disorder; Minimally Invasive; Model Organism; Molecular Marker; Multi-Photon; Novel; Older Adult; Older Person; Outcome Forecast; Patient Population; Phase 1 Study; Phase 1 Trial; Phase I Trial; Protocol, Phase I; Prototype; Public Health Relevance; Ratiometric; Renal; Senior Citizen; Success; Two-Photon; Urinary; Vascular