Single Molecule Detection of Oligomers in Cerebrospinal Fluid
Access to Data and Biospecimens, 2016
We have developed a novel method for detecting aggregations (clumps) of proteins (specifically, alpha-synuclein) in the spinal fluid of those with Parkinson's disease (PD). We seek to evaluate the potential of this technique in samples from PD participants and healthy participants with the primary aim of identifying a useful biological marker of Parkinson's and its progression.
We hypothesize a sub-type of misfolded alpha-synuclein protein will both be detectable in spinal fluid of those with PD and closely reflect the pathogenesis of the disease.
Aggregates of the alpha-synuclein protein have long been established as important in Parkinson's disease. Using novel techniques, we now have the capacity to measure these aggregates at the single molecular level, thus providing potential unparalleled resolution. With this technique, we hope to show clear differences between those with PD and those without PD (case-control study design) and therefore evaluate whether this may be a useful biological marker of disease.
Impact on Diagnosis/Treatment of Parkinson's Disease:
If a biologically-useful biomarker is developed, it will have profound impacts in trial design, principally by enabling earlier identification of the disease and thereby improving power. This could have a huge benefit on the timescales and size of studies, therefore massively reducing the cost.
Next Steps for Development:
If it is determined that this technique can be harnessed to specifically identify the toxic form of a protein (hypothesized to be the oligomer), then it will be important in the next stage to evaluate its specificity for sub-types of parkinsonism and scale up the method.
Galton Professor of Genetics UCL, Professor of Neurogenetics and Clinical Neurology at UCL Institute of Neurology
Location: London, United Kingdom