What does BioMOx involve?

The Oxford Study for Biomarkers in MND – BioMOx – was a ground-breaking platform to follow a cohort of MND patients through their individual disease pathway and generate a range of candidate biomarkers to improve the diagnostic pathway and therapy development. It was funded through a partnership of the Motor Neurone Disease Association & Medical Research Council Lady Edith Wolfson Fellowship scheme.

Phase 1 (2009-13) studied more than 70 MND patients (of all disease sub-types, including PLS) for one day every six months, comparing them with healthy individuals of a similar age. In this way, BioMOx was a ground-breaking idea to follow a cohort of MND patients through their individual disease pathway, and generate a range of candidate biomarkers.

Phase 2 (2013-18) was designed to develop these candidates further towards use in the clinic, including looking for the very earliest detectable changes in those with hereditary forms of MND.

This required the study of several groups:

  • MND patients
  • People suspected to have MND but not yet diagnosed
  • People with conditions that look like MND but are known to be something else
  • Healthy relatives of MND patients where the condition runs in the family, particularly if there is a known genetic mutation
  • Healthy volunteers of similar age to MND patients

What are biomarkers?
MND (ALS) research is held back in part by the lack of an early diagnostic test and predictable markers of the progression of the disease – these are called biomarkers. Patients still wait too long for a certain diagnosis of MND, and it is possible that future drugs may need to be given at much earlier stages to be most effective. Clinical trials currently require lengthy study times to get a clear answer, and don’t always account for the variability of the disease between patients. The worldwide MND research community and the MND Association UK are united in their desire to improve this situation:

“We regard this study as extremely important and it is a great opportunity for people with MND to be actively involved with research. With your support this study has the potential to play a pivotal role in the discovery of a biomarker for MND.” said the Motor Neuron Disease Association.

Biomarkers might be changes visible on research MRI scans, or substances measurable in the blood or spinal fluid. These would need to be specific for MND and change in a predictable way with the type and progression of the disease. The discovery of such biomarkers could change the way that clinical trials are organised, allowing beneficial drugs to be identified more quickly and ineffective drugs to be discounted sooner. It is also hoped that biomarker discovery, by speeding up diagnosis, could allow drugs to be given at a much earlier stage, which might improve their effectiveness. Biomarkers specific for certain patterns of disease spread in MND would permit improved care planning and might further understanding of disease mechanisms, with the potential to provide new drug development targets.

The BioMOx study is now closed to recruitment, but for information about ongoing biomarker studies at Oxford, including the AMBRoSIA project, please click on the links.

Selected publications of results:

  1. Impaired corticomuscular and interhemispheric cortical beta oscillation coupling in amyotrophic lateral sclerosis
  2. Increased cerebral functional connectivity in ALS: A resting-state magnetoencephalography study
  3. Cerebrospinal fluid macrophage biomarkers in amyotrophic lateral sclerosis
  4. The two-year progression of structural and functional cerebral MRI in amyotrophic lateral sclerosis
  5. Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis
  6. Quantitative FLAIR MRI in Amyotrophic Lateral Sclerosis
  7. Defective cholesterol metabolism in amyotrophic lateral sclerosis
  8. Altered cortical beta-band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis
  9. Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS
  10. A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis
  11. Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk
  12. Eye-tracking in amyotrophic lateral sclerosis: A longitudinal study of saccadic and cognitive tasks
  13. CSF neurofilament light chain reflects corticospinal tract degeneration in ALS
  14. The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis
  15. What does imaging reveal about the pathology of amyotrophic lateral sclerosis?
  16. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis
  17. Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis
  18. Multiple kernel learning captures a systems-level functional connectivity biomarker signature in amyotrophic lateral sclerosis
  19. Diagnostic accuracy of diffusion tensor imaging in amyotrophic lateral sclerosis: a systematic review and individual patient data meta-analysis.
  20. Myelin imaging in amyotrophic and primary lateral sclerosis
  21. Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS
  22. Fractional anisotropy in the posterior limb of the internal capsule and prognosis in amyotrophic lateral sclerosis
  23. Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis
  24. Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis
  25. The diagnostic pathway and prognosis in bulbar-onset amyotrophic lateral sclerosis
  26. Pattern of spread and prognosis in lower limb-onset ALS
  27. CSF chitinase proteins in amyotrophic lateral sclerosis
  28. UFLC‐Derived CSF Extracellular Vesicle Origin and Proteome
  29. Regional thalamic MRI as a marker of widespread cortical pathology and progressive frontotemporal involvement in amyotrophic lateral sclerosis
  30. Towards a TDP-43-Based Biomarker for ALS and FTLD