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Investigating Therapeutic Effect of Different Antioxidants in Friedreich’s Ataxia (FRDA)

Friedreich’s Ataxia (FRDA) is an inherited neurodegenerative disorder caused by epigenetic silencing of the frataxin gene. It is the most common inherited ataxia, affecting 1:50,000 Caucasians, and is characterised by neurodegeneration, cardiomyopathy, diabetes mellitus and skeletal deformities. There is currently no effective treatment for FRDA. However, there have been a number of recent clinical trials to investigate FRDA therapy, including the use of antioxidants, frataxin stabilisers, enhancers and replacement, iron chelators, and gene therapy. Thus far, although some positive biochemical effects have been observed in preclinical and clinical research using these disease-modifying agents, none have shown a significant capacity to ameliorate the neurological symptoms associated with FRDA. Therefore, there is still a high unmet clinical need to identify a more effective FRDA therapy. Aberrant frataxin expression in FRDA results in increased oxidative stress and mitochondrial dysfunction, driving disease progression. Recent studies in FRDA cells indicated that frataxin deficiency inhibits Nrf2 (Nuclear factor (erythroid-derived 2)-like 2 and impairs antioxidant defences, leading to an elevation in lipid peroxidation. Thus, a number of experimental avenues have been pursued in order to trigger the Nrf2 antioxidant pathway and prevent lipid peroxidation. The aim of the Ataxia lab is to investigate the molecular mechanisms of FRDA with the view to provide novel therapeutic strategies for FRDA diagnosis and treatment. In particular, this project will focus on investigating the therapeutic efficacy of different antioxidants to ameliorate the molecular and biochemical disease effects of FRDA using cell culture and mouse models.

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  1. Contact the supervisor by email or phone to discuss your interest and find out if you woold be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
  2. Click on the 'Apply here' button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
  3. Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.

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This is a self funded topic

Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.