BREONICS, INC. — Department of Health and Human Services SBIR Phase I: NIAID

Description

DESCRIPTION provided by applicant The goal of this project is address a large unmet medical need by providing more kidneys for transplant For the andgt patients with end stage renal disease in the U S the pool of cadaveric kidneys has remained stagnant over the past decade As a result the dialysis population is expected to reach andgt million patients in the next decade at an aggregate cost of andgt $ trillion USD We intend to use BREONICSandapos warm Exsanguinous Metabolic Support EMS perfusion technology C that supports ex vivo oxidative metabolism as the platform to deliver Mesoblast Inc andapos s non immunogenic mesenchymal precursor cells MPCs technology that is in late Phase clinical trials to mediate the repair of warm ischemically damaged human kidneys The combination of EMS technology that is awaiting FDA approval to begin clinical trials in kidney transplantation with the MPCs technology to repair ischemically damaged kidneys will provide for significant expansion of the cadaveric renal allograft pool by making it feasible to access cadaveric donors kidneys that today are never considered for transplantation in the U S because they are considered to be too damaged By localizing the MPCs within damaged kidneys during ex vivo EMS perfusion the repair processes will be potentiated The targeting of MPCs directly to the kidney will result in higher intrarenal concentrations of the paracrine and endocrine effects than can be achieved with the dilution effects that occur with systemic administration of MPCs The MPCs will be fluorescently labeled and tested in a paired human kidney model A dose escalation study will be performed where one kidney will be EMS perfused without stem cells while the paired human kidney will be perfused with the MPCs for hours of ex vivo EMS perfusion Evaluation of the repair potential will include the extent and reversibility of proteinuria to identify the loss recvery of cell surface polarity glomerular filtration rate DNA synthesis cytoskeletal regeneration chemokine cytokine synthesis and histologic evaluations Once the optimized dose of MPCs per gram of kidney is identified we will perform in depth studies to more fully characterize the repair processes for the human kidneys using the labeled MPCs to determine deposition and any retention within the renal parenchyma synthesis renal markers of injury repair and characterization of the recovered MPCs following perfusion to determine the phenotype and synthetic functions following the hours of EMS perfusion of the human kidneys Significant to our project is the observation that MPCs mediated paracrine effects occur within hours a period that corresponds to our proposed hours of ex vivo EMS perfusion Mesoblast Inc a public company is well positioned to commercialize the technology developed from this project We believe an allograft treated with MPCs will obtain regulatory approval as transplantable because the MPCs are not immunogenic do not integrate or survive within the body do not form teratomas and have an established safety profile If successful this approach to expanding organ donor criteria will positively impact the organ shortage PUBLIC HEALTH RELEVANCE We are proposing a feasibility study to repair human kidneys with damage so severe that they cannot be used today for a kidney transplant This project represents a potential solution to the world wide shortage of transplantable kidneys for the more than Americans being kept alive by hemodialysis We will use BREONICSandapos acellular near normothermic perfusion technology as a platform to deliver Mesoblastandapos s non immunogenic mesenchymal stem cells to potentiate the repair human kidneys