Rapid and Ultra-sensitive Quantitation of Disease-associated and Synuclein Seeds in Brain and Cerebrospinal Fluid by Syn RT-QuIC

Study Rationale:                   

The diagnosis and treatment of Parkinson’s disease (PD) would be aided by the availability of direct and highly sensitive tests for the abnormal clusters of the protein a-synuclein (αSyn) that appears to cause the disease. Two such tests have been reported by other laboratories, but these tests take 5-13 days to perform in the laboratory. We have developed a similar test that takes only 1-2 days and allows measurement of relative amounts of αSyn clusters. We will further evaluate our new test using the MJFF/NINDS BioFIND set of cerebrospinal fluid samples from PD patients and controls.

Hypothesis:

We hypothesize that our new Parkinson’s test, called αSyn RT-QuIC, will show high diagnostic accuracy for PD, while being much faster than previously described αSyn RT-QuIC, or related, assays.

Study Design:

The BioFIND sample set will be sent to us blinded (coded) so that we do not know ahead of time which samples came from PD cases and which from healthy controls. We will test the samples and send the results back to MJFF/NINDS for decoding. Analysis of the results will allow us to determine the diagnostic sensitivity (the proportion of PD cases giving positive test results) and specificity (the proportion of healthy control cases giving negative test results).

Impact on Diagnosis/Treatment of Parkinson’s disease:              

If our new αSyn RT-QuIC maintains the diagnostic performance that we have already seen in our initial studies to date, it should facilitate early and accurate diagnosis of PD. Such diagnoses may allow appropriately targeted treatments to begin earlier. In addition, such testing should improve clinical trials of new treatments by improving the selection of cases and controls, and allowing levels of abnormal αSyn to be compared in treated and untreated patients over the course of a trial.

Next Steps for Development:

If our testing of the BioFIND samples set gives promising results, we will expand the testing to even larger and more diverse sample sets in order to further evaluate the diagnostic and prognostic utilities of the αSyn RT-QuIC testing of cerebrospinal fluid. We are also training other laboratories to perform their own independent αSyn RT-QuIC  testing to encourage broader implementation and innovation.