May 14, 2019
Approximately 60,000 Americans are diagnosed with Parkinson disease (PD) each year, according to the Parkinson Foundation. Diagnosing PD can be challenging, as there are no objective tests to make a definitive diagnosis.
However, new research presented at the American Neurological Association’s 143rd Annual Meeting shines light on a potential noninvasive diagnostic test. For their study, lead author Dr Suman Dutta, senior author Dr Gal Bitan, and colleagues examined whether α‐synuclein could distinguish between patients with multiple system atrophy (MSA) and those with PD via a simple blood test.
Gal Bitan, PhD, is Professor of Neurology and a Member of the Brain Research Institute and Molecular Biology Institute at the University of California, Los Angeles.
Can you explain your findings and what they mean for practicing neurologists and Parkinson specialists?
The main advantage of our study is that for the first time we have been able to distinguish between PD and MSA with high sensitivity and specificity using a blood test. There have been other studies that got similar sensitivity and specificity, but they used cerebrospinal fluid analysis, which is much more invasive, refused by many patients, and is particularly problematic if we want to follow disease progression.
Our study is the first, I believe, that could achieve such a high degree of separation between the 2 diseases using a blood test. We achieved it by using a methodology that has been spearheaded by other groups in the dementia field. The methodology uses exosomes—nanovesicles shed by virtually all cells. From the blood serum we isolated the exosomes that came from 2 types of brain cells: neurons and oligodendrocytes. Then, in the exosomes from both cell types, we measured the protein believed to be the main culprit in both PD and MSA: α-synuclein. Each cell type alone offered moderate separation, but the combination of both allowed the groups to separate with high sensitivity and specificity.
Our study was medium size—50 patients with PD, 30 patients with MSA, and 50 healthy controls. The data need to be validated in independent cohorts and larger numbers of patients. If the data are reproducible, the test could be offered to neurologists and movement-disorders specialists everywhere to help in getting to the correct differential diagnosis.
Do you think the outcomes would differ for patients with familial vs sporadic PD?
This is a very interesting question that we would like to address in the future. Because α-synuclein accumulation is a pathologic component of almost every patient with PD, the test is likely applicable to patients with both familial and sporadic disease. However, there may be subtle, yet significant differences that may help us gain a better understanding of the underlying mechanisms of the disease.
What is the next step in your research?
The first step is to validate the findings in additional cohorts, which we are working on. We are also testing more biomarkers (i.e., in addition to α-synuclein) with the hope to increase the accuracy of the test above the current 90% and get it as close as possible to 100%.
A very exciting future direction is using the methodology for following the progression of the different diseases, which will allow us to test the effect of new therapy in clinical trials. We have already started doing that in both pre-clinical and clinical experiments. Finally, the methodology can be readily applicable to additional diseases. First and foremost on our radar are other parkinsonian disorders, such as progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies, but there are many others to which this methodology could be applied.
What is the unanswered question regarding PD you hope to answer?
My ultimate goal is to be able to answer the question posed by each individual who starts to show suspicious symptoms—“What is causing my symptoms?”—with 100% accuracy and to be able to measure precisely if a particular medication/treatment is improving the condition of each patient. It is obviously a tall order, but it is a good goal to have. I will be happy with any progress we can make toward this goal.
To read more about Dr Bitan’s study, click here.
Dutta S, del Rosario I, Paul K, et al. α‐synuclein in brain‐derived blood exosomes distinguishes multiple system atrophy from Parkinson's disease. Paper presented at: American Neurological Association’s 143rd Annual Meeting; October 21-23; Atlanta, GA.https://doi.org/10.1002/ana.25331. Accessed October 25, 2018.