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Research paper

Hyperactivity of mTORC1- and mTORC2-dependent signaling mediates epilepsy downstream of somatic PTEN loss

PTEN loss hyperactivates both mTORC1 and mTORC2; rapamycin rescues epilepsy and early mortality in mouse models even after epilepsy is established; for PTEN/PIK3CA/AKT disorders, dual PI3K/mTOR or AKT inhibitors may outperform mTORC1-selective rapalogs.

Indexed context

Lasser M, et al.

ptenpi3k-akt-mtormtor-inhibitionprecision-medicine

Markdown path

content/research/papers/2024-lasser-pten-mtorc1-mtorc2.md

Findings

PTEN loss hyperactivates both mTORC1 and mTORC2; rapamycin rescues epilepsy and early mortality in mouse models even after epilepsy is established; for PTEN/PIK3CA/AKT disorders, dual PI3K/mTOR or AKT inhibitors may outperform mTORC1-selective rapalogs.

Why it may matter for Levi

Directly frames the mTOR-directed therapy treatment item. If a PTEN/PI3K/AKT variant is identified in Levi, the literature supports considering dual-pathway inhibitors rather than empiric rapalogs; empiric mTOR-directed therapy without molecular confirmation is not supported.

Paper text

Hyperactivity of mTORC1- and mTORC2-dependent signaling mediates epilepsy downstream of somatic PTEN loss

Lasser M, et al. — eLife (2024). https://pmc.ncbi.nlm.nih.gov/articles/PMC10942640/

Findings summary

PTEN loss hyperactivates both mTORC1 and mTORC2; rapamycin rescues epilepsy and early mortality in mouse models even after epilepsy is established; for PTEN/PIK3CA/AKT disorders, dual PI3K/mTOR or AKT inhibitors may outperform mTORC1-selective rapalogs.

Relevance to Levi

Directly frames the mTOR-directed therapy treatment item. If a PTEN/PI3K/AKT variant is identified in Levi, the literature supports considering dual-pathway inhibitors rather than empiric rapalogs; empiric mTOR-directed therapy without molecular confirmation is not supported.

Provenance

  • Ingested 2026-04-16 as part of the batch literature pass supporting the Root Cause Theories, diagnostics, and treatments workspaces.
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