# Targeting OGDH for Glioblastoma Therapy

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $246,750

## Abstract

Glioblastoma WHO IV (GBM) is the most common primary brain tumor with about 8500
cases diagnosed each year in the United States. Within a time frame of roughly one year
almost all patients succumb to this detrimental disease despite treatment. Therefore,
novel, ideally tumor specific approaches are necessary to combat these tumors. Tumor
growth is ultimately determined by nutrients. We have shown before that lactate
accumulates to a significant amount in GBMs and that lactate rescues a broad range of
GBM cells from nutrient deprivation mediated cell death, which is dependent on the
tricarboxylic acid (TCA) cycle. Through interrogation of genome wide pooled CRISPR
library screens performed in GBM models, we unexpectedly found that OGDH (2-
oxoglutarate dehydrogenase), a key enzyme of the TCA-cycle, is a critical driver gene
for glioblastoma growth. Using a clinically validated OGDH inhibitor (CPI-613) we found
that this drug extended animal survival. We will take these findings further and extend
our research in the underlying mechanisms and will assess the overall hypothesis that
the standard of care is enhanced by loss of function of OGDH, involving appropriate
pharmacodynamics and pharmacokinetic analyses. The knowledge generated from this
proposal has the potential for high-impact paradigm changing science, knowledge that
will ultimately and hopefully at some point allow us to defeat this detrimental disease.

## Key facts

- **NIH application ID:** 10904486
- **Project number:** 1R21NS137660-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MARKUS D SIEGELIN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,750
- **Award type:** 1
- **Project period:** 2024-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904486

## Citation

> US National Institutes of Health, RePORTER application 10904486, Targeting OGDH for Glioblastoma Therapy (1R21NS137660-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10904486. Licensed CC0.

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