What we do
About our project
FXTAS is a late onset neurodegenerative disorder causing tremor, ataxia, brain pathology, cognitive loss, dementia and early death in some individuals carrying a fragile X premutation. The hallmark of FXTAS neuropathology in postmortem brain tissue is the presence of ubiquitin-positive intranuclear aggregates in both neurons and astrocytes. FXTAS is hypothesized to be caused by a gain-of-function mechanism, including protein sequestration model and toxic polypeptide model. Since both the gene and the pathogenic trigger (RNA containing an expanded CGG repeat between 50-200) are known, this disorder represents a promising candidate for the development of targeted treatments.
The overall aim of our research is to understand the molecular processes involved in FXTAS disease pathology and to develop therapeutic intervention strategies.
Our research focus
Our research focus on a mechanism of toxicity that is triggered by CGG repeat associated non-AUG initiated (RAN) translation. Please check this animation of RAN translation:
Currently, there is a need to define critical ages when pathology begins, development windows when the disease may be halted or reversed, and the cellular and molecular mechanisms that may serve as therapeutic targets for patients with FXTAS. To address these important needs, we have developed powerful state-of-the-art in vitro and in vivo models of FXTAS, including: primary neurons, mouse and zebrafish models.
Funds & Grants
- 2014 ERA-Net project E-Rare (project coordinator)
Preclinical approaches towards therapeutic intervention for FXTAS.