Everolimus for the treatment of neuropsychological deficits in tuberous sclerosis complex: findings from the TRON multicentre randomised controlled trial

Saxena A, Drew CJ, Cannings-John R, Pickles T, Mills LJ, McDermott E, Angel L, McNamara R, Smalley M, Randell E, Joss SK, …, Sampson JR · 2026 · Journal of medical genetics · Atlas ID SAX2026

What this study shows

In a multicentre RCT of TSC patients (n=38 randomised, 2:1 everolimus:placebo), 24 weeks of everolimus produced similarly large 'responder' rates for neuropsychological improvement as placebo (87% vs 75%), suggesting large practice/placebo effects rather than a clear drug benefit on cognition -- despite everolimus's established efficacy for TSC tumours and epilepsy. Adverse events were more frequent with everolimus (88% vs 61.5%).

Cited on mTOR drugs in development: AV078

Abstract

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Mammalian target of rapamycin (mTOR) inhibitors are effective treatments for tumours and epilepsy in tuberous sclerosis complex (TSC). This study aimed to determine the effects of the mTOR inhibitor everolimus and a placebo on neuropsychological functioning in TSC. Individuals with TSC aged 16-60 years and IQ>60 who scored <=5th percentile in one or more of 10 memory or executive function variables were randomised 2:1 to 24 weeks everolimus or placebo and retested at baseline and 4, 12, 24 and 36 weeks.

Read the full abstract on PubMed →

At a glance

Evidence type	H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type	2 - Human Clinical Trial
Model system	Human (TSC patients, aged 16-60, RCT)
Journal	Journal of medical genetics
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1136/jmg-2026-111529 · PMID 42562625

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Everolimus (mTOR inhibitor) vs placebo, 24 weeks, randomised 2:1
Target	mTOR (mTORC1)
Model	Human (TSC patients, aged 16-60 years)
Effect	No clear benefit of everolimus over placebo on neuropsychological function; both arms showed large responder rates (87% vs 75%), likely reflecting practice/placebo effects rather than a true drug effect

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question Brain-penetrant mTOR inhibition clears aggregates in models, but human dosing has not been shown to reach the brain — and mTORC2 is needed for memory in mice.

Cite this paper

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Saxena, A., Drew, C. J., Cannings-John, R., Pickles, T., Mills, L. J., McDermott, E., Angel, L., McNamara, R., Smalley, M., Randell, E., Joss, S. K., Donnelly, D. E., Davies, D. M., Owen-Jones, E., Kirby, N., de Vries, P. J., Hood, K., & Sampson, J. R. (2026). Everolimus for the treatment of neuropsychological deficits in tuberous sclerosis complex: findings from the TRON multicentre randomised controlled trial. Journal of medical genetics. https://doi.org/10.1136/jmg-2026-111529

@article{SAX2026,
  author       = {Saxena, A. and Drew, C. J. and Cannings-John, R. and Pickles, T. and Mills, L. J. and McDermott, E. and Angel, L. and McNamara, R. and Smalley, M. and Randell, E. and Joss, S. K. and Donnelly, D. E. and Davies, D. M. and Owen-Jones, E. and Kirby, N. and de Vries, P. J. and Hood, K. and Sampson, J. R.},
  title        = {{Everolimus for the treatment of neuropsychological deficits in tuberous sclerosis complex: findings from the TRON multicentre randomised controlled trial}},
  journal      = {Journal of medical genetics},
  year         = {2026},
  doi          = {10.1136/jmg-2026-111529},
  note         = {PMID: 42562625},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record SAX2026) [Data set]. https://mtor-atlas.org/study/SAX2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SAX2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SAX2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SAX2026/},
  doi          = {10.5281/zenodo.22059963}
}

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