Development of the nephroplate: a high-throughput kidney-on-a-chip platform for identifying chronic kidney disease therapies

Ended Project Grant Awarded Last action

Award ID
R44DK127659
Recipient
Awarding agency
Obligated
$3,500,000

Award facts

Completion date
Originally
Funding agency
National Center for Advancing Translational Sciences National Institutes of Health, Department of Health and Human Services
Place of performance
Maryland, USA

Award details come from USAspending.gov.

Description

Abstract
With chronic kidney disease on the rise, IT is imperative that we identify better treatment strategies to avoid a healthcare crisis. Current therapeutic interventions address patient symptoms rather than the underly cause and thereby do not substantially slow disease advancement. Developing drugs to treat the underlying cause or disorder leading to CKD will address this need, however such advancements have been hampered by the lack of in vitro human kidney models used in the drug development pipeline. Thus, an in vitro model which accurately mimics individual human ckds and can be screened for disease-relevant therapeutic interventions is urgently needed to identify targeted CKD interventions. This phase II sbir is a continuation of a successful phase i and a collaborative effort between mimetas and the children's hospital of LOS angeles (chla). Together we will focus on addressing the market need for a 3D kidney-on-a-chip platform, called the nephroplate for use in drug discovery. The nephroplate will enable the evaluation of kidney function in response to circulating and genetic factors of CKD-causing disorders. For this phase II project, we will focus on glomerulopathies where we have previous experience, alport syndrome and membranous nephropathy, and where there is a high demand from nephroplate customers, diabetic nephropathy and APOL1 nephropathy. For each CKD, we will characterize phenotype (immunostaining, western blot, rnaseq) and glomerular filtration function by measuring the passage of fluorescent albumin and the trans-epithelial electrical resistance (teer) within the microfluidic system. All systems will be validated to high-throughput drug screening standards. Filtrate from the glomerulus-on-a-chip cultures will be transferred to the proximal tubule-on-a-chip cultures to evaluate the impact of glomerular disease on proximal tubules. Finally, proteomics will be performed on the glomerular and proximal tubule filtrate to identify potential biomarkers specific to each CKD. Once executed these studies will establish the nephroplate as a high-throughput drug screening platform for use by pharmaceutical companies and academic laboratories to investigate mechanisms of CKD diseases and ultimately identify disease-specific therapeutics.

Transactions

Action Obligated Date
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Amendment $500,000
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Amendment $1,000,000
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Original award $1,000,000
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Quick answers

Who received award R44DK127659?

R44DK127659 was awarded to Mimetas US Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on September 28, 2020.

How much is award R44DK127659 worth?

$3,500,000 has been obligated on R44DK127659.

Which agency awarded R44DK127659?

National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) awarded R44DK127659, with funding from National Center for Advancing Translational Sciences (National Institutes of Health).

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