To assess therapeutic effects of the natural neurosteroid, Allopregnanolone, on the neuropsychiatric manifestations of the late adult onset neurodegenerative disease, Fragile X-associated tremor/ataxia syndrome (FXTAS).

FXTAS is a neurodegenerative disease affecting carriers of the FMR1 premutation, a 55-200 CGG trinucleotide repeat expansion on the X chromosome, and is characterized by progressive kinetic tremor, ataxia, dementia, Parkinsonism and neuropsychiatric symptoms. Currently no disease modifying treatment has been found. We hypothesize Allopreganolone, a natural neurosteroid and GABA-A potentiator shown to induce oligodendrogenesis and hippocampal neurogenesis, may improve the cognitive and neuropsychiatric symptoms in FXTAS given it’s neuroregenerative properties.

Six men with FXTAS (ages 57 -79) underwent weekly Allopregnanolone infusions in an open label trial for three months. Doses started at 2mg and were gradually increased to 6mg infusions. A battery of neuropsychiatric pre- and post- treatment measurements were collected and analyzed for changes, including the Behavioral Dyscontrol Scale-II (BDS-2) and Cambridge Neuropsychological Test Automated Battery (CANTAB), that measured executive function, attention and memory.

Most patients showed improvements in mental state, executive function, auditory, visual, immediate and delayed memory. Outcome measures such California Verbal Learning Test (CVLT-II), Mini-mental status exam (MMSE) and Beck Anxiety Inventory (BAI), showed changes that were not significant. Improvements on BDS-2 and CANTAB Paired Associates Learning achieved statistical significance with 100% and 83% patients improving after infusion respectively (p = 0.009 and p = 0.042).