Friedreich's Ataxia, also known as FA, is a progressive, neurological movement disorder affecting multiple organs and cell types. FA affects approximately 1 in 40,000-50,000 people and onset is typically between 10-15 years of age. Initial symptoms include unsteady posture and frequent falling, with progressive difficultly in walking with gait and limb ataxia. Heart complications and diabetes are also often involved in the course of the disease.
The Friedreich's Ataxia Alliance at Oxford (FA Alliance), established via a philanthropic gift, brings together researchers and clinicians from across the University of Oxford and beyond to harness the potential of the Oxford-Harrington Rare Disease Centre to develop new therapies to cure or treat FA.
We advance FA therapeutic development programmes, foster collaboration and facilitate partnerships with the existing global FA research community, coordinating closely with the Friedreich's Ataxia Research Alliance (FARA) and Ataxia UK.
Prof Esther Becker
Associate Professor of Neurobiology
Prof Esther Becker's lab focuses on genetic disorders of the cerebellum with a particular interest in the ataxias. In an effort to develop improved human and disease-relevant models to study cerebellar disorders and develop treatments, Esther's group has developed a method to generate cerebellar neurons and organoids from human induced pluripotent stem cells.
Prof Paul Brennan
Professor of Medicinal Chemistry
Prof Paul Brennan's Medicinal Chemistry group discovers chemical leads for drug discovery, with particular focus on epigenetics and dementia. Paul has funded projects to develop drugs to treat FA, and in 2020, with fellow Alliance members Richard Wade-Martins and Andrea Németh, Paul published a paper describing increased frataxin expression in FA patient cells upon inhibition of the SUV4-20 H1 histone methyltransferase.
Dr Mariana Conceicao
Senior Postdoctoral Scientist and Team Leader
Dr Mariana Conceicao has vast experience in nanotechnology, gene therapy and molecular medicine. Mariana is currently leading work involving extracellular vesicles and adeno-associated viral vectors as gene delivery systems in Prof Matthew Wood's laboratory.
Prof Mark Crabtree
Associate Professor of Cardiovascular Biochemistry
Prof Mark Crabtree's research group focuses on understanding the mechanisms of nitric oxide and redox signalling in molecular models of cardiovascular disease. Mark has developed metabolomic and proteomic approaches to understand the impact of redox alterations in models of cardiovascular homeostasis and disease, which he will apply to FA models.
Prof John Davis
ARUK Oxford Drug Discovery Institute Director
Prof John Davis leads the Alzheimer’s Research UK Oxford Drug Discovery Institute. John has over 25 years of drug discovery expertise from target to phase 2a and has helped steer a dozen drug candidates into development and to four phase 2 proof of concepts. He brings his extensive experience to direct towards finding a novel therapy to treat or cure FA.
Prof Helen Dawes
Professor of Clinical Rehabilitation
Prof Helen Dawes’s ambition is to enable people living with conditions affecting their movement to be able to move more. Her main research focus is translation of individualised rehabilitation into clinical practice, with innovation of methodologies for the delivery and evaluation of interventional outcomes. She uses a wide variety of technologies to monitor movement and posture, with the intention of developing technologies that are transferable between diseases and affordable to ensure global applicability.
Dr Andrew Douglas
Consultant and Honorary Senior Clinical Lecturer in Clinical Genetics
Dr Andrew Douglas’s principal research interests include genomics and transcriptomics, RNA splicing, oligonucleotide therapeutics, neuromuscular and neurodegenerative disorders. The overall goals of Andrew’s research are to understand neurogenetic disorders, to improve genetic diagnostics through RNA analysis and to develop effective genetic treatments through RNA-based therapeutics. He has previously worked on delivering emerging therapies for Duchenne Muscular Dystrophy to the brain.
Prof Natalia Gromak
Associate Professor in Pathology
Prof Natalia Gromak’s group are interested in an unusual DNA/RNA structure called R-loops. Natalia’s team investigate the molecular basis of neurodegenerative diseases associated with pathological R-loops, including FA and Fragile X syndrome. The group are striving to understand how the GAA repeat expansion in the frataxin gene leads to its transcriptional repression, with a view to developing new therapeutic approaches to treat FA.
Dr Francois Halloy
Postdoctoral Research Fellow
Dr Francois Halloy's research interests lie at the nexus of chemistry and biology, with a concentration on the development of oligonucleotide formulations for genetic disorders. His focus is on the development of molecular shuttles for the delivery of oligonucleotide therapeutics through the blood-brain barrier.
Prof Andrea Németh
Professor and Consultant in Neurogenetics
Prof Andrea Németh’s main focus is to understand the genetic basis of ataxias. Andrea’s lab has developed next generation sequencing for diagnostics in ataxias and retinal degeneration, and has identified several new cerebellar ataxia disorders. Andrea collaborates on projects developing objective smartphone-based gait biomarkers; investigating imaging biomarkers for Friedreich’s Ataxia (FA); and investigating small molecule treatment for FA. Andrea set up the Oxford Ataxia Clinic in 1999 and has continued to run this clinic ever since, routinely seeing patients with FA referred from a wide geographical region.
Prof Carlo Rinaldi
Associate Professor and Honorary Consultant Neurologist
The overall purpose of Prof Carlo Rinaldi’s research is to reduce the burden of hereditary neurological disease. This goal is pursued through three strategic aims: (1) identification of genes associated with neurological diseases, (2) advancement of the current understanding of the molecular mechanisms of pathogenesis in these diseases, and (3) development of effective treatments for hereditary neurological diseases. Together with Prof Andrea Nemeth, Carlo runs the Oxford Neurogenetics Clinical service, where he diagnoses and treats patients with FA.
Dr Tom Roberts
Senior Postdoctoral Scientist and Team Leader
Dr Tom Roberts’s research interests include neuromuscular disorders, RNA biology, extracellular nucleic acids, biomarkers, epigenetics, and gene/oligonucleotide therapies. Tom employs highly novel approaches to develop therapeutics to upregulate frataxin expression by targeting unique genetic regulatory sequences.
Prof Angela Russell
Professor of Medicinal Chemistry
Prof Angela Russell’s work focuses on the discovery of new drug targets and mechanisms, and the translation of these findings into new clinical candidates. Through several successful multidisciplinary research collaborations, Angela’s team works in a range of therapeutic areas including identifying small molecules to upregulate utrophin for the treatment of Duchenne Muscular Dystrophy (DMD), new anti-cancer agents and agents to stimulate endogenous cell populations for regenerative medicine.
Prof Chris Toepfer
Associate Professor of Cardiovascular Science
Prof Chris Toepfer’s background is in cardiac muscle regulation in health and disease. He is currently supported by a Wellcome and Royal Society Sir Henry Dale Fellowship and a British Heart Foundation Centre of Research Excellence Intermediate Transition Fellowship in Oxford to investigate the role of thick filament variants in hypertrophic cardiomyopathy (HCM). The laboratory focuses on CRISPR/Cas-9 engineering of human induced pluripotent stem cells. These cells can be differentiated into cardiomyocytes, which are used to model human heart disease in a dish.
Dr Miguel Varela
Senior Postdoctoral Scientist and Team Leader
Dr Miguel Varela is an expert on microsatellite repeat expansion disorders, of which Friedreich’s Ataxia is one. His main focus is on pre-clinical translational research and is especially interested in degenerative disorders of the nervous system and muscle. Miguel leads a number of public-funded projects and collaborative programs with pharmaceutical companies, where his group explores the efficacy of novel therapeutic targets, and facilitates the in vivo delivery of oligonucleotides and RNA-based therapeutics to improve the biodistribution of these drugs.
Prof Richard Wade-Martins
Professor of Molecular Neuroscience
Prof Richard Wade-Martins’s research is focused on better understanding the molecular mechanisms underlying neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease and FA. His work combines the development of improved induced pluripotent stem cell (iPSC)-derived neuronal culture models with studies on human post-mortem brain tissue and the generation and analysis of novel transgenic and knockout mouse models. His work focuses on the study of the functional and genetic mechanisms underlying key neurodegeneration disease loci. Together with Prof Paul Brennan, Richard is developing epigenetic-targeting small molecules to regulate frataxin gene expression.
Prof Matthew Wood
Professor of Neuroscience
Prof Matthew Wood’s research is in the field of gene therapy for degenerative disorders of the nervous system and muscle. The main focus is the investigation of novel therapeutic approaches utilising short nucleic acids to target messenger RNA. Current work is investigating the potential of single-stranded antisense oligonucleotides for the modification of mRNA splicing, for example in Duchenne muscular dystrophy. In addition, the potential of double-stranded RNA for gene silencing, known as RNA interference (RNAi), is being investigated for the silencing of target genes and mutant alleles both in muscle and in the nervous system. These approaches have great potential as therapeutic agents for currently untreatable disorders such as FA.
Prof Wyatt Yue
Visiting Professor of Structural Biology at Oxford
Prof Wyatt Yue is a structural biologist who specialises in the use of structural, biochemical and chemical biology approaches to study diverse metabolic protein families in the human genome, with the aim of deciphering the molecular mechanism of human inherited diseases at the protein level. Through collaborations with clinicians and pharma partners, his team aims to translate basic science into design of small molecule therapeutics for rare diseases with unmet need. Wyatt published the structure of the human frataxin-bound iron-sulfur cluster assembly complex, providing insight into its activation mechanism and potential for therapeutic development.
If you have any queries about the FA Alliance, or are doing research relevant to finding a cure for FA, please do get in touch with Geoff Denwood, Research Facilitator for the Oxford-Harrington Rare Disease Centre.