# Molecular mechanisms of podocyte injury in FSGS

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $411,127

## Abstract

SUMMARY
Chronic kidney diseases affect more than 700 million people worldwide, and are a frequent cause
of kidney failure and death. A key event leading to kidney failure is filter damage, caused by the
loss of podocytes. This is a cause of a kidney disease known as Focal segmental
Glomerulosclerosis (FSGS). Despite the growing prevalence of kidney diseases, there are
currently no FDA approved therapies to prevent the loss of podocytes. The goal of this grant
application is to gain a deep understanding of the molecular mechanisms involved in podocyte
injury related to the BRAF signaling pathway, so that it may be targeted for therapeutic benefit.
We started with a rare genetic kidney disease caused by mutations in an enzyme called PDSS2.
Interestingly, we found that the loss of function of this enzyme causes podocytes to die, resulting
in FSGS. We subsequently found that a key molecule in preventing podocyte death is BRAF and
a small molecule that activates BRAF, called GDC-0879, can protect podocytes from cell death.
In fact, GDC-0879 was able to protect podocytes from several injuries including toxic lipids and
other stress-causing molecules. Most excitingly, we now have evidence that GDC-0879 protects
mice from podocyte injury and the resulting kidney filter damage (called proteinuria). Here, we will
explore the precise molecular mechanisms involved in BRAF-related podocyte injury, and the
potential for GDC-0879 to become a treatment for FSGS.
Successful completion of this work may provide a new, much needed treatment for FSGS and
chronic kidney diseases, and one that may be easily brought to the clinic, since GDC-0879 is
already an FDA approved drug for other indications.

## Key facts

- **NIH application ID:** 10120140
- **Project number:** 2R01DK095045-08A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Anna Greka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $411,127
- **Award type:** 2
- **Project period:** 2014-03-10 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120140

## Citation

> US National Institutes of Health, RePORTER application 10120140, Molecular mechanisms of podocyte injury in FSGS (2R01DK095045-08A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10120140. Licensed CC0.

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