Study Rationale:
Despite several published studies using different anti-alpha-synuclein antibodies, to date no lab-based methods have been able to reliably identify Parkinson’s disease (PD) cases from healthy controls in biopsies from the colon. Thus, in order to reliably determine the potential of assessing alpha-synuclein in colon biopsies as a diagnostic indicator a person has PD, there is a need for the development of novel antibodies that detect a signal in most pateints with PD (sensitivity) and do not detect any signal in individuals who do not have PD (specificity). To address this need, we have developed the 5G4 antibody that does not bind to the healthy form of alpha-synuclein (that is expressed in all people with and without PD), but is highly specific for disease-associated forms of alpha-synuclein.
Hypothesis:
We hypothesize that staining colon biopsy tissues with 5G4 will be able to sensitively and specifically discriminate individuals with PD from those without PD.
Study Design:
We will obtain colon biopsy tissues collected from 58 individuals with PD and 21 control volunteers through the Michael J. Fox Foundation-sponsored Systemic Synuclein Sampling Study (S4). We will stain the tissues with the 5G4 antibody and, under a microscope, we will rate tissue from all cases as either positive or negative for the presence of disease associated alpha-synuclein. We will perform an analysis to determine the sensitivity (percentage of PD cases with a positive signal) and the specificity (percentage of control cases with a negative signal).
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Currently there is no accurate diagnostic test for PD. Diagnosis relies upon a clinical examination, which can be inaccurate. Having an accurate diagnostic test will allow better communication with patients; could possibly be used as an outcome measure in clinical trials looking at ways to prevent the build-up of disease-associated forms of alpha-synuclein; and, finally, could potentially identify people in very early stages of disease when new treatments may be most effective.
Next Steps for Development:
If successful, this study would pave the way for developing a diagnostic test for PD. It would also support further studies looking at the presence of 5G4 staining in individuals at high risk for developing PD to determine if this can identify people in very early stages of disease. As many countries have screening programs for colon cancer, collecting colon biopsy tissues to check for disease-associated forms of alpha-synuclein in large numbers of the population is very feasible, adding to the possible impact of our study.