Research paper
Adjunctive antiepileptic efficacy and safety study of mTOR inhibitors in children with tuberous sclerosis complex
Meta-analysis of mTOR inhibitor (everolimus, sirolimus) efficacy in TSC. Quantifies seizure reduction, SEGA volume reduction, skin lesion response, and adverse event profile.
Ding Y, et al.
Markdown path
content/research/papers/2026-ding-mtor-inhibitors-tsc-meta-analysis.mdFindings
Meta-analysis of mTOR inhibitor (everolimus, sirolimus) efficacy in TSC. Quantifies seizure reduction, SEGA volume reduction, skin lesion response, and adverse event profile.
Why it may matter for Levi
Template for what mTOR inhibitor therapy might look like if Levi is confirmed to have a mosaic PI3K-AKT-mTOR variant. The quantified efficacy data here are the evidentiary basis for advocating rapalog therapy in a confirmed mTORopathy context. Strengthens - without changing - the existing differential ranking.
Ding et al. (2026) — mTOR inhibitors in TSC pediatric epilepsy (meta-analysis)
Source
- Seizure 138:84-92, 2026.
Why in corpus
2026 meta-analysis confirming sirolimus and everolimus (mTOR inhibitors) as effective adjunctive antiepileptic therapy in children with TSC. Directly relevant to the mosaic PI3K-AKT-mTOR hypothesis for Levi as a precision-treatment prior.
Key findings
- Both sirolimus and everolimus effective as adjunctive antiepileptic therapy in children with TSC.
- Efficacy independent of whether seizure onset occurred before or after age 2.
- Adverse effects common but mostly mild.
Levi-relevant takeaways
- Strongest 2026 evidence that rapalog therapy works for epilepsy in pediatric mTOR-axis disease. If a mosaic PI3K-AKT-mTOR variant is ever identified in Levi, this meta-analysis is the primary support for moving to rapalog therapy.
- Not applicable empirically — empiric rapalog without a confirmed molecular diagnosis would be off-label and unsupported.
- Reinforces the priority of the mosaic-sensitive tissue-based PI3K-AKT-mTOR panel: a positive finding transforms treatment options.
- Efficacy across age-of-onset strata means a positive finding in Levi (now 5.5 years) would still be therapeutically actionable — rapalog benefit is not limited to infantile-onset patients.