Elucidation of the metabolic signature of Friedreich's ataxia

In recent years, there has been a growing interest in the use of metabolomics in neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. However, insufficient resources have been dedicated to studying alterations in the levels of small molecules, metabolites, and lipids in Friedreich’s ataxia (FRDA). Therefore, we aim to identify unique metabolic signatures of FRDA human and mouse model samples using mass spectrometry–based metabolomics approaches.

Our approach to studying the role of metabolic dysfunction in FRDA disease pathogenesis is threefold:

1. We aim to evaluate the intracellular oxidative stress and mitochondrial health and function and to assess the bioenergetics profiles of FRDA cell lines using tools to analyze oxidative metabolism;
2. We aim to investigate the effect of frataxin reduction on metabolic pathways involved in mitochondrial function and energy metabolism in FRDA samples using several highly-sensitive mass spectrometric-based methods; and lastly
3. We aim to delineate the impact of targeting relevant metabolic enzymes to rescue the deficits of central metabolism in FRDA.

We expect that the findings of this proposal will provide a unique opportunity to devise novel therapeutic strategies for FRDA patient diagnosis and treatment through targeting their unique metabolism.

Meet the Principal Investigator(s) for the project

Dr Sara Anjomani Virmouni - Sara was educated at the University of Tehran, where she was awarded a Bachelor degree in animal sciences with first class honours in 2008. She moved to the Biosciences Division at Brunel University London to undertake her MSc in Molecular Medicine and Cancer Research. In 2011, Sara was awarded a scholarship by the School of Health Sciences and Social Care, Brunel University London to investigate Friedreich’s ataxia (FRDA) disease mechanisms using FRDA mouse models and cells under the supervision of Dr Mark Pook. She finished her PhD in 2013 and was awarded Vice Chancellor's best doctoral research prize. She continued her work as a Postdoctoral Research Fellow at Brunel University London to study the efficacy and tolerability of histone methyltransferase (HMTase) inhibitors in FRDA. Sara then joined the Institute of Cancer Research (ICR) as a Postdoctoral Research Fellow in 2015 to study the signaling and metabolic networks in breast cancer. In 2018, she was awarded a research grant from Friedreich’s Ataxia Research Alliance (FARA) and joined Brunel University London as a Principal Investigator to investigate the metabolic signatures of FRDA. Subsequently, she was appointed as a lecturer in Biosciences. Her research continues to investigate FRDA disease pathogenesis and therapy and identify the most effective therapy for FRDA.

Project last modified 21/11/2023