Clinical Research

Multi-centre Huntingdon’s Disease (TRACK-HD)

Sarah Tabrizi, Roger Ordidge, David Thomas.

TRACK–HD is a multi-centre, multi-national, prospective, observational biomarker study of pre-manifest and early Huntington’s disease (HD) with a control group of volunteers not carrying the HD mutation. The goal of the project is to contribute essential methodology that will form the basis for neuroprotective trial in pre-manifest and early HD by determining the individual and joint utility of a selected set of clinical and biological outcome measures. The study includes clinical and biological markers including neuropsychiatric, cognitive, quantitative motor, oculomotor, imaging markers and laboratory biomarkers. The study is being carried out at London (UCL), Paris, Leiden and Vancouver.

Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS)

Madhan Kolappan, Siddharthan Chandran, Claudia Wheeler-Kingshott,. David Thomas, David Miller.

The aim of the study (MSCIMS) is to investigate a type of stem cell for the treatment of Multiple Sclerosis. The primary aim is to establish that these cells can be used safely, but the trial also aims to explore any potential effects they may have on the condition. This will be measured by looking at the brain, optic nerve (a nerve from the eye) and retina (the back of the eye) using various tests.

Cross-sectional 3T study of glutamate in the corticospinal tract of patients with multiple sclerosis.

Olga Ciccarelli, Claudia Wheeler-Kingshott, Roger Ordidge, Alan Thompson

Glutamate excitotoxity may be one of the main mechanisms of the damage to neurons and oligodendrocytes in MS lesions. During inflammation, glutamate is released into the extracellular space in large quantities. Accordingly, the levels of glutamate in cerebrospinal fluid of patients with relapsing-remitting MS have been reported to be higher in patients assessed during relapse than those in patients examined during the stable phase of the disease. Moreover, it has been recently found using single voxel spectroscopy that glutamate increases in both the acute enhancing lesions and normal-appearing white matter (NAWM) of patients with MS. These observations link increased glutamate with patients’ clinical status. Thus, in this project, we will measure glutamate in the NAWM of the corticospinal tract (CST) in patients with MS. We will also compare the concentration of other metabolites (such as N-acetyl aspartate (NAA) and inositol (Ins)) along the motor tract between patients and controls. Finally, we will assess whether glutamate and any other metabolite in the CST correlates with disability and brain atrophy and/or cortical thinning.

We expect to find increased glutamate, reduced or normal NAA, and increased Ins, in the CST of MS patients compared to controls. The glutamate levels will be greater in patients with higher motor disability and in those with greater thinning of the motor cortex. The glutamate concentration measured at baseline in the group of acute patients will predict the development of disability and axonal loss (e.g. brain atrophy and cortical thinning) at 6 months in those patients who will perform a follow-up study.