In a recent Lancet Neurology study from the Parkinson’s Progression Markers Initiative (PPMI), researchers have shown that a biomarker test can accurately identify people who are in the earliest stages of Parkinson’s disease. This is a hugely exciting moment for EPND; as an initiative aiming to accelerate large-scale biomarker research, we were delighted to see a new development that many are calling a game-changer for the Parkinson's disease field.

In a special Parkinson’s Awareness Month research blog, we present the key results of this ground-breaking, large-scale biomarker study. Read on to learn more!

For decades, Parkinson’s disease diagnosis has relied primarily on the assessment of neurological symptoms, such as tremor, balance problems, and gait changes. However, the biological processes that drive Parkinson’s can start many years before the appearance of symptoms. Accurately detecting these biological changes could have huge benefits; earlier diagnosis, more tailored treatments, and – perhaps – prevention of Parkinson’s disease.

We now know that Parkinson’s disease (PD), like other neurodegenerative disorders such as Alzheimer’s disease, is driven by the accumulation of misfolded proteins in the brain. In PD, alpha-synuclein is the key culprit; alpha-synuclein aggregates in the substantia nigra are a pathological hallmark of PD, linked to the loss of dopaminergic neurons and the development of motor deficits. Until now, clinical assays for alpha-synuclein have only been tested in small, independent studies. In a landmark discovery for the Parkinson’s disease field, PPMI researchers have shown that the alpha-synuclein Seed Amplification Assay can accurately detect pathology in cerebrospinal fluid (CSF) samples from a large, multi-national cohort of people with, or at-risk of PD.

PPMI is a world-leading study collaborating with global partners to create a robust, open-access data set and biosample library to accelerate PD research and innovation. Launched in 2010 by the Michael J. Fox Foundation together with academic and industry partners, PPMI innovates at scale: the study involves 50 clinical sites in 12 different countries. A number of these sites feature in our Catalogue: notably, cohorts led by Kathrin Brockmann at the University of Tübingen, and Michele Hu’s Oxford Parkinson’s Disease Center discovery cohort, at the University of Oxford. As a longitudinal, observational natural history study, PPMI enrolls people at all stages of PD from prodromal to moderate disease, aiming to evaluate the progression of clinical features, imaging outcomes, and biomarkers.

In their Lancet Neurology article, a team of researchers co-led by Andrew Siderowf (University of Pennsylvania Perelman School of Medicine) and Luis Concha-Marambio (Amprion) analysed samples from 1,123 participants in the PPMI cohort. Participants were recruited at 33 centres across the US, UK and Europe, undergoing CSF and blood sampling as well as clinical and imaging assessments. Seed Amplification Assays (SAA) were used to measure the amount of alpha-synuclein in CSF samples from participants, 545 of whom had a PD diagnosis; 163 of whom were healthy controls; and 310 of whom were asymptomatic carriers of gene variants linked to PD.

Findings revealed that the biomarker test was highly accurate, correctly identifying 87.7% of people with PD. People with prodromal PD – individuals who have non-motor symptoms such as loss of smell or sleep disturbance – were identified with 86% accuracy. This indicates that people with prodromal PD have abnormal alpha-synuclein before detectable changes in clinical or imaging tests. They observed some variability among genetic subgroups (people carrying different gene variants), particularly in people with the LRRK2 variant. Importantly, the test was abnormal in only 5% of people without PD, confirming the high sensitivity and specificity of the SAA assay.

In a press release for the Lancet Neurology article, co-lead author Andrew Siderowf, outlined some of the clinical implications of the new study, saying: “Recognising heterogeneity in underlying pathology among patients with PD has been a major challenge. Identifying an effective biomarker for PD pathology could have profound implications for the way we treat the condition, potentially making it possible to diagnose people earlier, identify the best treatments for different subsets of patients, and speed up clinical trials.”

Congratulations to the authors!

Read the press release for their Lancet Neurology article, here.