Research Grant Award

Lay Abstract of Kyle Bryant Translational Research Award Funded in Mid – 2007

Principal Investigator: Nuri Gueven, PhD, Senior Research Officer

Queensland Institute of Medical Research
Use of a novel catalytic antioxidant, CTMIO, in a GAA repeat mouse model of FRDA Project Objectives

Since the pathology of Friedreich's Ataxia (FRDA) is associated with increased levels of oxidative stress and antioxidant therapy for this disease shows promising results, it is imperative to develop improved antioxidants that display high bioavailability, high antioxidant activity without major side effects.

The overall aim of this project is to test if the novel nitroxide antioxidant 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) can alleviate the pathological changes associated with an established GAA-repeat-mouse model of Friedreich’s Ataxia (FRDA). We have used CTMIO before to markedly increase tumor latency in a mouse model of ataxia-telangiectasia (A-T). CTMIO also effectively corrected neurobehavioral function in Atm mice unlike the antioxidants used in FRDA mouse models and patients. CTMIO belongs to class of so called catalytic antioxidants. In contrast to radical scavengers such as vitamins, catalytic antioxidants can repeatedly inactivate reactive species and are thus much more potent than scavengers (up to 10000 times). This study will determine whether compounds such as CTMIO can be used as a therapeutic approach for FRDA in the future. It will also test the mode of action of CTMIO in this animal model with respect to markers of oxidative stress, macromolecular damage and changes in cellular signaling. As such, this project contributes to our understanding of the role of oxidative stress in multiple aspects of FRDA and the results of this study could directly lead to improved treatment options of FRDA.