Vorinostat Corrects Cognitive and Non-Cognitive Symptoms in a Mouse Model of Fragile X Syndrome.
Level 5 - mechanism / opinion, no new human data
Animal model and in vitro laboratory study (Fmr1 knockout mice and cultured neurons).
PubMed 34791268 · doi:10.1093/ijnp/pyab081
What was done
Researchers evaluated the therapeutic potential of the FDA-approved drug vorinostat for Fragile X syndrome (FXS) following transcriptome-based prediction. They assessed vorinostat in Fmr1 knockout mice across cognitive tests (object location memory, passive avoidance memory) and non-cognitive behavioral assays (repetitive behavior, social interaction, open field hyperactivity). They also tested its effect on protein synthesis in cultured Fmr1 knockout hippocampal neurons.
What was found
The abstract reports no numerical values. Vorinostat restored object location memory and passive avoidance memory in Fmr1 knockout mice. It also corrected autism-associated repetitive behaviors and social interaction deficits, and dampened hyperactivity in the open field test center. However, vorinostat did not correct the abnormally elevated protein synthesis in cultured Fmr1 knockout hippocampal neurons.
Why it matters
This study provides preclinical evidence supporting the potential repurposing of vorinostat for Fragile X syndrome, while demonstrating that behavioral correction can occur without resolving elevated basal protein synthesis.
Limits
The study is restricted to an animal model and in vitro cell culture, providing no direct human clinical evidence. The abstract does not report sample sizes, dosage details, or quantitative effect sizes with measures of variance.
Cited by
- supports Fragile X syndrome model mice exhibit social withdrawal behavior when placed in a cage with other mice.