Progetto: Beta-band EMG-EMG coherence: a novel, painless and simple screening test for the onset of corticospinal tract disease/dorsal root ganglionopathy in Friedreich’s Ataxia

Principal-Investigator: Dr Mark R Baker, Institute of Neuroscience, Newcastle University, UK
Co-Investigators: Professor Patrick F Chinnery, Institute of Genetic Medicine and Professor Stuart Baker, Institute of Neuroscience, Newcastle University, UK

Friedreich’s Ataxia (FA) is an autosomal recessive hereditary ataxia with a very high carrier rate (between 1/60 and 1/90), caused by unstable GAA trinucleotide repeat expansions within the first intron of the frataxin (FXN) gene. FXN is clearly important in normal mitochondrial function; reduced levels of functioning FXN results in mitochondrial iron accumulation and the accumulation of multiple mitochondrial DNA deletions.
In patients the lack of functioning FXN typically manifests as a progressive neurological syndrome with features of dorsal root ganglionopathy, and degeneration and atrophy of the dorsal columns, spinocerebellar tracts, corticospinal tracts and dentate nuclei.
With the increasing understanding of the molecular basis of FA and the move to potential neuroprotective therapies, there is an increasing need for non-invasive measures of neuronal degeneration and loss. Such measures must be capable of detecting subclinical pathological changes in individuals with a genetic diagnosis who have not yet developed extensive neuronal loss, thus permitting early intervention.
We propose to develop just such a measure using surface electromyogram (EMG) recorded using a novel handheld device developed in our research laboratory. This test is painless and therefore easy to use in children. It is also extremely simple to perform and could be delivered by any healthcare professional.
We plan a longitudinal study of adult and paediatric patients with FA. Repeated surface EMG recordings will be made at intervals of 3 months, in addition to routine clinical neurophysiological tests, which will include nerve conduction studies (NCS), sensory evoked potentials (SEPs) and transcranial magnetic stimulation (TMS) motor evoked potentials (MEPs). Finally, these electrophysiological measures will be compared with measures of frataxin (FXN) expression and functional assays of frataxin deficiency (i.e. mitochondrial dysfunction and degeneration)
In this project we aim to develop a simple, painless, inexpensive and portable electro-diagnostic screening test of subclinical sensory neuronopathy/corticospinal tract degeneration in Friedreich’s Ataxia and to assess what happens to this electrophysiological measure over time in a longitudinal study and thus to establish whether it can be used as a marker of progression (or surrogate outcome measure) for future therapeutic trials.

Finanziamento: 149,358 $ ( 1anno da 17 Novembre 2014) Co-finanziato da FARA e Ataxia UK