Research, Appendix & References Research Read more Recent progress There have been a number of advances in the last few years in the identification of new genes causing specific ataxias, largely due to recent developments in gene sequencing technologies. Worldwide research using next generation sequencing and whole exome/genome sequencing has led to the identification of many new forms of ataxia and these developments are beginning to be translated into clinical services available to patients34. Research is also progressing in understanding the basic biological mechanisms underlying the ataxias and many therapeutic targets have now been identified. This has then lead to pre-clinical studies of potential disease-modifying drugs in animal and cell models, and encouragingly a number of clinical trials in people with ataxia are ongoing. A summary of recent published trials is found below (Table 14). This is included to illustrate that a number of types of drug trials have taken place. There are also many more trials in the pipeline, either to confirm the results of pilot studies listed or exploring new potential treatments (see www.clinicaltrials.gov). Although there are as yet no approved treatments for the majority of progressive ataxias, it is hopeful that due to this increased activity approved treatments will become available soon. Table 14: List of recent published trials in ataxia Medication Type of ataxia Type of drug/mode of action Idebenone279–286 Friedreich’s ataxia Antioxidant CoQ10/Vitamin E287, 288 Friedreich’s ataxia Antioxidant Carnitine/creatine289 Friedreich’s ataxia Antioxidant Deferiprone290 Friedreich’s ataxia Iron chelator Deferiprine and idebenone291 Friedreich’s ataxia Iron chelator & antioxidant Triple therapy Idebenone, deferiprone and riboflavin292 Friedreich’s ataxia Iron chelator & antioxidants EPO293–295 Friedreich’s ataxia Increases frataxin Carbamylated EPO296 Friedreich’s ataxia Increases frataxin A0001297 Friedreich’s ataxia Antioxidant Nicotinamide298 Friedreich’s ataxia Increases frataxin RG2833299 Friedreich’s ataxia Increases frataxin Interferon gamma300,301 Friedreich’s ataxia Increases frataxin Resveratrol302 Friedreich’s ataxia Antioxidant Riluzole303,304 Mixed ataxias Drug repurposing/unknown mechanism Lithium305,306 SCA2, SCA3 Drug repurposing/ reduces protein aggregates Varenicline307–313 SCA3, SCA14, Friedreich’s ataxia, Fragile X tremor/ataxia Drug repurposing/unknown mechanism Memantine314, 315 Fragile X tremor/ataxia Drug repurposing/unknown mechanism Research has also focused on the development of tools to measure the severity and progression of ataxia for use in trials such as validated ataxia-specific rating scales (detailed in Table 15, below). Table 15: Ataxia rating scales International cooperative ataxia rating scale (ICARS)316 All ataxias Scale for the Assessment and Rating of Ataxia (SARA)148,317 Spinocerebellar ataxias/Friedreich’s ataxia Friedreich’s ataxia rating scale (FARS)318 Friedreich’s ataxia Friedreich’s ataxia impact scale (FAIS)319 Friedreich’s ataxia Inventory of non-ataxia signs (INAS)320 Progressive ataxia disorders Databases and natural history data is being collected by networks of researchers worldwide and this has been of immense use in the design and implementation of clinical trials317,321. Due to all these encouraging developments, and the incentives provided in legislation on research in rare disease generally, pharmaceutical and biotech companies are now engaging more in ataxia research and indeed many research trials are being run by pharmaceutical companies, often in collaboration with university researchers and patient groups, such as Ataxia UK. Participating in research studies It is good clinical practice to offer patients the opportunity to take part in research projects. For information on research studies recruiting participants in the UK contact Ataxia UK, the ataxia charity who supports people with ataxia and works towards developing treatments for the ataxias. Ataxia UK For more information on ataxia research contact Ataxia UK, which provides up-to-date information for patients and healthcare professionals on developments in the ataxia field, including opportunities for patients to take part in research. Healthcare professionals are encouraged to join Ataxia UK’s Medical Registry and/or Researcher’s Registry and receive regular electronic newsletters with information on any trials recruiting participants. Information on ataxia conferences and ataxia training days is also provided. Ataxia UK also provides funding for research projects and facilitates research (eg: by organising ataxia conferences/meetings, helping to recruit participants in research projects and advising on the research landscape) and is willing to work in partnership with interested parties from academia, industry, patient groups and other stakeholders (contact [email protected]). Appendix Read more A list of neurologists at Ataxia UK Accredited Specialist Ataxia Centres and other Centres of expertise*. The following are adult neurologists (and clinical geneticists where indicated). Specialist Ataxia Centres Prof Marios Hadjivassilliou Ataxia UK Accredited Ataxia Centre, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust Glossop Road, Sheffield S10 2JF Dr Paola Giunti Ataxia UK Accredited Ataxia Centre, National Hospital for Neurology and Neurosurgery Queen Square, London WC1N 3BG Prof Rita Horvath Ataxia UK Accredited Ataxia Centre,Newcastle upon Tyne Hospitals NHS trust, Royal Victoria Infirmary Queen Victoria Road, Newcastle upon Tyne NE1 4LP Other Centres Dr George Tofaris & Prof Andrea Nemeth (Clinical Geneticist) Ataxia Clinic John Radcliffe Hospital, Oxford OX3 9DU Dr Richard Davenport Western General Hospital Crewe Road South, Edinburgh EH4 2XU Dr Rajith de Silva Queen’s Hospital Rom Valley Way, Romford, Essex RM7 0AG Dr John Ealing Salford Royal NHS Foundation Trust Stott lane, Salford, Greater Manchester M6 8HD Dr Nick Fletcher The Walton Centre for Neurology and Neurosurgery, NHS Trust, Lower Lane, Liverpool L9 7LJ Dr Simon Hammans St Richard’s Hospital Spitalfield Lane, Chichester, West Sussex PO19 6SE Dr Paul Hart St Helier Hospital Wrythe Lane, Carshalton, Surrey SM5 1AA Dr John McKinley & Dr Seamus Kearney Royal Victoria Hospital Grosvenor Road, Belfast BT12 6BA Dr Neil Robertson & Dr Mark Wardle University Hospital Wales Heath Park, Cardiff CF14 4XN Dr Alastair Wilkins Southmead Hospital Bristol BS10 5NB Professor Nicholas Wood Institute of Neurology Queen Square, London WC1N 3BG Dr Paul Worth Cambridge University Hospitals NHS Foundation Trust Hills Road, Cambridge CB2 0QQ Paediatric neurologists & paediatric clinical geneticists Prof Peter Baxter: Sheffield Children’s Hospital, Western Bank, Sheffield, S10 2TH Prof Andrea Nemeth (Clinical geneticist, see details above) Dr V Ramesh: Great Northern Children’s Hospital, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP *Please note that this is a list of specialists known to Ataxia UK and to the Guideline Development Group and is not an exhaustive list. 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