What type of study is this?

This is a Cohort Study study (also classified as: Experimental Study).

September 17, 2025

GABA production induced by imipridones is a targetable and imageable metabolic alteration in diffuse midline gliomas

Key Points

An increase in GABA levels is a key marker of response to imipridones in diffuse midline gliomas.
This study reveals that imipridones can enhance response through autocrine GABA signaling mediated by the GABAB receptor.
Using 1H-MRS and biochemical methods demonstrated the metabolic changes in preclinical DMG models.
The findings hold promise for precision metabolic therapy and imaging for children with challenging brain tumors.

Abstract

Motivation: Diffuse midline glioma (DMG) are fatal brain tumors in children. The imipridones ONC201 and ONC206 have shown promise in DMG treatment, but efficacy is limited, and biomarkers of treatment response are lacking. Goal(s): To determine whether imipridones induced 1H-MRS-detectable metabolic alterations in preclinical DMG models in vivo. Approach: Usage of 1H-MRS and biochemical methods in patient-derived DMG cells and tumor xenografts. Results: We show that an increase in 1H-MRS-detectable GABA is a unique biomarker of response to imipridones. Importantly, GABA induces autocrine GABA signaling via the GABAB receptor that can be exploited to enhance response to imipridones in vivo. Impact: We have developed an integrated metabolic therapy and 1H-MRS-based imaging strategy for diffuse midline glioma patients. Clinical translation of our studies has the potential to enable precision metabolic therapy and imaging for children battling this devastating form of brain cancer.

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