ArticleNeurobiology of disease2011
A pulse rapamycin therapy for infantile spasms and associated cognitive decline.
Article in Neurobiology of disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Pathogenetic mechanisms of focal cortical dysplasia.Epilepsia · 2014Pooled it
- The multiple hit model of infantile and epileptic spasms: The 2025 update.Epilepsia open · 2025Article
- Epileptic drop attacks: More than just atonic seizures.Epilepsia open · 2025Article
- Role of hippocampus in epileptogenesis: new insights in the cross-talks between the underlying mechanisms.Acta neurologica Belgica · 2025Review
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Efficacy and tolerability of celastrol and edaravone in the multiple-hit rat model of infantile spasms.Epilepsy & behavior : E&B · 2025Article
- Tau Phosphorylation Patterns in the Rat Cerebral Cortex After Traumatic Brain Injury and Sodium Selenate Effects: An Epibios4rx Project 2 Study.Journal of neurotrauma · 2024Article
- Revisiting the concept of drug-resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force.Epilepsia · 2023Article
- Cortical Parvalbumin-Positive Interneuron Development and Function Are Altered in the APC Conditional Knockout Mouse Model of Infantile and Epileptic Spasms Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review
- Antiepileptogenic effects of rapamycin in a model of infantile spasms due to structural lesions.Epilepsia · 2021Article
- Rapamycin, but not minocycline, significantly alters ultrasonic vocalization behavior in C57BL/6J pups in a flurothyl seizure model.Behavioural brain research · 2021Article
- Article
- A team science approach to discover novel targets for infantile spasms (IS).Epilepsia open · 2021Article
- A Warburg-like metabolic program coordinates Wnt, AMPK, and mTOR signaling pathways in epileptogenesis.PloS one · 2021Article
- The link between brain acidosis, breathing and seizures: a novel mechanism of action for the ketogenic diet in a model of infantile spasms.Brain communications · 2021Article
- Microglial mTOR is Neuronal Protective and Antiepileptogenic in the Pilocarpine Model of Temporal Lobe Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Epileptic spasms in individuals with Down syndrome: A review of the current literature.Epilepsia open · 2020Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Infantile spasms are seizures manifesting within a spectrum of epileptic encephalopathies of infancy that often lead to cognitive impairment. Their current therapies, including adrenocorticotropic hormone (ACTH), high dose steroids, or vigabatrin, are not always effective and may be associated with serious side effects. Overactivation of the TORC1 complex of the mTOR pathway is implicated in the pathogenesis of certain genetic and acquired disorders that are linked with infantile spasms, like tuberous sclerosis. Here, we tested the therapeutic potential of rapamycin, a TORC1 inhibitor, as a potential treatment for infantile spasms in the multiple-hit rat model of ACTH-refractory symptomatic infantile spasms, which is not linked to tuberous sclerosis. Rapamycin or vehicle was given after spasms appeared. Their effects on spasms, other seizures, performance in Barnes maze, and expression of the phosphorylated S6 ribosomal protein (pS6: a TORC1 target) in the cortex, using immunofluorescence, were compared. Rapamycin suppressed spasms dose-dependently and improved visuospatial learning, although it did not reduce the frequency of other emerging seizures. High-dose pulse rapamycin effected acute and sustained suppression of spasms and improved cognitive outcome, without significant side effects. Therapeutically effective rapamycin doses normalized the pS6 expression, which was increased in perilesional cortical regions of pups with spasms. These findings support that pathological overactivation of TORC1 may be implicated in the pathogenesis of infantile spasms, including those that are not linked to tuberous sclerosis. Furthermore, a high-dose, pulse rapamycin treatment is a promising, well tolerated and disease-modifying new therapy for infantile spasms, including those refractory to ACTH.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.