# Ion-channel targeted therapy for progressive kidney diseases

> **NIH NIH R01** · BROAD INSTITUTE, INC. · 2020 · $384,750

## Abstract

PROJECT SUMMARY
Progressive proteinuric kidney diseases are on the rise worldwide with more than 500
million people affected, and yet no effective therapies exist to halt their progression to
kidney failure. High blood pressure and diabetes remain the biggest drivers of progressive
kidney diseases worldwide. One big challenge is that the specific molecules and kidney
cells involved in progression of kidney diseases remain poorly understood.
Our recent work funded by this grant revealed two such molecules, Rac1 and TRPC5, as
responsible for the injury and death of precious kidney cells called podocytes. Loss of
podocytes resulted in proteinuria, the hallmark of a broken kidney filter barrier and ultimate
kidney failure. Funded by this grant, we also discovered a TRPC5 blocker, called AC1903,
which can prevent Rac1-TRPC5 from injuring podocytes. In two rat models of a kidney
disease called FSGS (Focal and Segmental Glomerulosclerosis), we showed that AC1903
prevented kidney filter damage and protected podocytes, making this an excellent
candidate for the development of a future therapy for patients.
However, at this time, it is not clear if AC1903 or other TRPC channel blockers can be
helpful in protecting the kidneys of patients with hypertension or diabetes-related kidney
diseases. Therefore, the goal of this revised competitive renewal application is to build on
our recent discoveries and perform careful and detailed studies in rat and mouse models
of progressive kidney diseases to gain further insight into the role of TRPC ion channels
and their blockers in the treatment of kidney diseases associated with hypertension and
diabetes. This work will pave the way for new therapies for kidney disease patients, which
are greatly needed.

## Key facts

- **NIH application ID:** 9957047
- **Project number:** 5R01DK099465-07
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Anna Greka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $384,750
- **Award type:** 5
- **Project period:** 2014-09-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957047

## Citation

> US National Institutes of Health, RePORTER application 9957047, Ion-channel targeted therapy for progressive kidney diseases (5R01DK099465-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9957047. Licensed CC0.

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