Targeting IDH and 2-HG: Mechanistic Links Between Tumor Biology and Seizure Activity

IDH-mutant diffuse gliomas represent a distinct subset of primary brain tumors, often affecting younger adults and characterized by a prolonged but clinically complex disease course. Beyond tumor progression, seizures remain one of the most disruptive and persistent features of the disease, reflecting both structural and biochemical changes within the brain.

During the 2026 AAN Annual Meeting in Chicago, Katherine B. Peters, MD, PhD, neuro-oncologist at Duke Health and professor of neurology and neurosurgery at the Preston Robert Tisch Brain Tumor Center, sat down with NeurologyLive® to discuss findings from the phase 3 INDIGO trial evaluating vorasidenib. The conversation highlights how advances in targeted therapy are beginning to reshape how clinicians think about both tumor control and neurologic symptoms.

In this episode, Peters outlines the biological underpinnings of seizure development in IDH-mutant glioma, focusing on the role of 2-hydroxyglutarate as a key oncometabolite. She explains how vorasidenib’s inhibition of mutant IDH enzymes may not only limit tumor growth but also reduce excitatory signaling within the brain, offering a dual mechanism that could impact both disease progression and seizure burden.