Research
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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 studies 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 research@ataxia.org.uk).


Appendix
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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. We would welcome contact from other neurologists with expertise in ataxia (email: research@ataxia.org.uk)


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This information is taken from Management of the ataxias - towards best clinical practice third edition, July 2016. This document aims to provide recommendations for healthcare professionals on the diagnosis and management of people with progressive ataxia. To view the full document, including references, click here.