Approximately 20 years ago clinicians made a striking observation: grandfathers of children with fragile X syndrome frequently displayed Parkinsonian-like phenotypes. Subsequent studies showed that a premutation of the FMR1 gene was the cause for this, as this results in the formation of aberrant proteins aggregates, cell damage and a disorder now called the Fragile X Tremor Ataxia Syndrome.

We investigate how the gene mutation and protein aggregates are damaging neuronal cells, particularly in determining their effects in brain regions that control cognitive and emotional behaviours. We have already shown that the damage is partially reversible, and are currently searching for suitable pharmacological interventions

The cerebellum is a site for neurodegeneration in FXTAS, involved in the observed motor deficits. The image shows the labelling of cells and neurites in a section of the cerebellum.



Castro H, Kul E, Buijsen RAM, Severijnen LWFM, Willemsen R, Hukema RK, Stork O, Santos M. Selective rescue of heightened anxiety but not gait ataxia in a premutation 90CGG mouse model of Fragile X-associated tremor/ataxia syndrome. Hum Mol Genet. 2017 Jun ;26(11):2133-2145.



ERARE funded research project Drug_FXSpremut

PI: Prof. Dr. Oliver Stork

Researcher: M.Sc. Emre Kul