Related Experiment Video
Updated: Jun 2, 2026
Repeated Transcranial Magnetic Stimulation Combined with Action Observation Training in Children with Spastic Cerebral Palsy
Published on: August 9, 2024
A pulse rapamycin therapy for infantile spasms and associated cognitive decline
Emmanuel Raffo1, Antonietta Coppola, Tomonori Ono
1Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx NY 10461, USA.
Insights
Rapamycin, a TORC1 inhibitor, effectively treats infantile spasms and improves cognitive function in a rat model. This promising therapy shows disease-modifying potential for infantile spasms, even those resistant to standard treatments.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Infantile spasms are severe epileptic encephalopathies causing cognitive impairment.
- Current therapies like ACTH and steroids have limited efficacy and side effects.
- TORC1 pathway overactivation is implicated in some infantile spasms, such as those in tuberous sclerosis.
Purpose of the Study:
- To investigate rapamycin, a TORC1 inhibitor, as a treatment for infantile spasms.
- To evaluate rapamycin's effects in a rat model of ACTH-refractory infantile spasms not linked to tuberous sclerosis.
- To assess rapamycin's impact on spasms, other seizures, cognitive function, and TORC1 pathway activity.
Main Methods:
- Administered rapamycin or vehicle to rats after spasm onset.
- Assessed spasm frequency, other seizure types, and visuospatial learning (Barnes maze).
- Quantified phosphorylated S6 ribosomal protein (pS6) expression in the cortex via immunofluorescence.
Main Results:
- Rapamycin dose-dependently suppressed infantile spasms and improved visuospatial learning.
- High-dose pulse rapamycin achieved sustained spasm suppression and cognitive improvement with no significant side effects.
- Effective rapamycin doses normalized elevated cortical pS6 levels in affected pups.
Conclusions:
- Pathological TORC1 overactivation contributes to infantile spasms, including non-tuberous sclerosis-associated forms.
- High-dose, pulse rapamycin is a well-tolerated, disease-modifying therapy for infantile spasms.
- Rapamycin offers a promising new treatment option for ACTH-refractory infantile spasms.
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.
