Researchers have discovered a potential biomarker that may indicate the progression of Parkinson’s disease. A recent study suggests that patients experiencing slower advancement of the disease exhibit significantly higher levels of a molecule known as ecto-GPR37 in their cerebrospinal fluid.
A group of researchers from the University of Barcelona and the Bellvitge Biomedical Research Institute (IDIBELL) has pinpointed a promising biomarker that could track the progression of Parkinson’s disease. This new study, featured in the NPJ Parkinson’s Disease journal, indicates that patients whose disease progresses slowly show a notable increase in the levels of ecto-GPR37 within their cerebrospinal fluid. These findings might greatly affect treatment strategies for individuals suffering from this neurodegenerative illness, characterized by motor symptoms such as tremors, stiffness, reduced movement, and balance issues.
According to Francisco Ciruela, a professor at the Faculty of Medicine and Health Sciences at the University of Barcelona and a member of both the Institute of Neurosciences (UBNeuro) and IDIBELL, “The study implies that this biomarker could help determine whether a patient’s disease will progress quickly or slowly. Clinically, being able to categorize these patients is essential as the management approach differs for those with slowly progressive Parkinson’s disease compared to those whose disease advances rapidly.”
Ciruela explains that individuals with rapid disease progression experience a swift onset and intensification of symptoms, including motor fluctuations and complications, as well as a greater chance of cognitive decline and psychiatric issues. Conversely, patients with slower progression typically have a gradual onset and worsening of symptoms, allowing them to maintain higher levels of functional ability for extended periods. Initially, these patients also display milder symptoms. “When disease progression is rapid, the outlook is poorer compared to slower progression, which can be managed similarly to chronic conditions, thus requiring less complex clinical management and providing a better prognosis,” notes Ciruela, who is at the forefront of this study.
The research was a collaborative effort involving professionals from the Spanish National Cancer Research Centre (CNIO), the Institute for Biomedical Research and Innovation in Cadiz, the Karolinska Institute in Sweden, the University of California in the USA, and King’s College London in the UK.
Study Utilizing Patient Samples from Various Neurodegenerative Diseases
This study builds on earlier research conducted in 2021, which indicated that ecto-GPR37, found on brain neuronal cells, could serve as a promising diagnostic biomarker for Parkinson’s disease. Ecto-GPR37 is a segment of a receptor known as GPR37, which has yet to have its neuronal functions or the specific molecule it binds to fully understood.
To affirm these findings and identify if this biomarker is unique to Parkinson’s disease, the research team analyzed GPR37 processing in the brain and measured ecto-GPR37 levels in the cerebrospinal fluid of patients with Parkinson’s, Alzheimer’s, and other neurodegenerative diseases that share clinical features with Parkinson’s, such as multiple system atrophy, corticobasal degeneration, and progressive supranuclear palsy. The researchers underline that, “despite some similarities, patients suffering from these conditions have different prognoses and do not respond to levodopa, the primary treatment for Parkinson’s disease. Thus, pursuing new biomarkers is critical for precise patient stratification, particularly during the early stages when making a diagnosis is more challenging.”
The analysis demonstrated that ecto-GPR37 levels increased solely in patients with slowly progressive Parkinson’s disease and not in those with rapid progression or in other diseases. “This observation indicates a potential link between GPR37 processing and expression to the rate of disease progression,” remarks Ciruela.
Scientists theorize that ecto-GPR37 exists in the brain because GPR37 receptors fragment upon reaching the surface of neurons, releasing ecto-GPR37 outside the cell. Consequently, in cases of slowly progressive Parkinson’s, ecto-GPR37 circulates in elevated concentrations within the cerebrospinal fluid, the fluid surrounding the brain and spinal cord.
Additionally, researchers observed distinct patterns of GPR37 processing and expression in the other neurodegenerative diseases studied. “This highlights GPR37’s potential role in differentiating between various neurodegenerative disorders,” adds Ciruela from the University of Barcelona.
Multicentre Study Across Europe
While the results from the University of Barcelona and IDIBELL team are promising, the researchers stress the necessity of validating ecto-GPR37’s role as a biomarker in more extensive patient cohorts from different hospitals. This will help confirm its clinical relevance, establish its reliability, and determine its applicability as a prognostic tool. Ciruela adds, “The next step is to design and implement a multicentre clinical project on a European scale to conduct the necessary validation study with Parkinson’s patients for clinical application.”
Moreover, with support from the Michael J. Fox Foundation, researchers have adjusted an assay to detect ecto-GPR37 in blood samples, simplifying analytical determination, as they conclude.
