Scientists have identified a potential biomarker for the progression of Parkinson’s disease.
According to the new study in which the discovery was made, patients with a slow progression of the disease would have a significant increase in the levels of a molecule called ecto-GPR37 in the cerebrospinal fluid.
What is discovered in this study could have important repercussions on the treatment of patients suffering from this neurodegenerative disease, characterized by movement disorders such as tremors, rigidity, slowness of movement or postural instability.
The study was conducted by a team of researchers from the University of Barcelona (UB) and the Bellvitge Biomedical Research Institute (IDIBELL), led by Josep Argerich from UB.
Francisco Ciruela, professor at the Faculty of Medicine and Health Sciences of the UB, member of the Institute of Neurosciences (UBNeuro) of the UB and member of the IDIBELL, explains that “what the study suggests is that this biomarker could serve to define whether the progression of the disease will be fast or slow. On a clinical scale, being able to perform this stratification is very important, because the management of patients with slowly progressive versus rapidly progressive Parkinson’s disease involves a different clinical approach.”
According to the researcher, in the case of patients with rapid progression, there is an accelerated onset and worsening of symptoms, motor fluctuations and complications, as well as an increased likelihood of cognitive impairment and psychiatric symptoms. In contrast, patients with slow progression have a more gradual onset and progression of symptoms and are able to maintain higher levels of functional capacity and for longer periods of time. Additionally, they often have milder symptoms, especially in the early stages. «If the disease progresses rapidly, the prognosis is worse than if it progresses slowly, as it can be managed more like a chronic disease. Consequently, patients with rapid progression require more complex clinical management than those with slow progression, who have a better prognosis”, underlines the UB professor, co-author of the study.
Researchers from Spain’s National Center for Cancer Research (CNIO) also participated in the work; the Cadiz Institute for Biomedical Research and Innovation in Spain; the Karolinska Institute of Sweden; the University of California in the United States and King’s College London in the United Kingdom.
This research is a continuation of a 2021 study by the same research team, which found that ecto-GPR37, found in neuronal cells in the brain, could be a promising candidate for a diagnostic biomarker for Parkinson’s disease. Ecto-GPR37 is a fragment of an orphan neuronal G protein-coupled receptor called GPR37. Although it is a receptor associated with Parkinson’s disease, its neuronal function and the endogenous ligand, i.e. the specific molecule to which it binds, are not yet known.
To validate previous findings and test whether this potential biomarker is specific to Parkinson’s disease, the researchers have now analyzed the processing of GPR37 in the brain and the presence of ecto-GPR37 in the cerebrospinal fluid of patients with Parkinson’s, Alzheimer’s, and also other diseases neurodegenerative. diseases with clinical features similar to Parkinson’s, such as multiple system atrophy, corticobasal degeneration and progressive supranuclear palsy. The researchers point out that “despite the similarities, patients suffering from these diseases have a different prognosis and do not respond to levodopa, the main treatment against Parkinson’s. “Therefore, exploring new biomarkers is essential to accurately stratify patients, especially in the early stages, when the diagnosis is more challenging”.
The results of this analysis show that ecto-GPR37 levels are increased only in patients with slowly progressive Parkinson’s disease, and not in the rapid type or in the rest of the diseases. “This finding suggests a possible connection between the processing and expression of GPR37 and the rate of disease progression,” says Francisco Ciruela.
According to scientists, the most plausible explanation for the presence of ecto-GPR37 in the brain is that, when the GPR37 receptor reaches the surface of neurons, it fragments and releases ecto-GPR37 outside the cell. As a result of this processing, in this type of slowly progressive parkinsonism, ecto-GPR37 would circulate in higher concentrations through the cerebrospinal fluid, the fluid that surrounds the brain and spinal cord.
On the other hand, the researchers also described a differential pattern of GPR37 processing and expression in the other neurodegenerative diseases analyzed. “This highlights the potential usefulness of GPR37 also for distinguishing between different neurodegenerative conditions,” adds the UB professor.
Although the results obtained by the UB and IDIBELL team are very promising, the researchers emphasize that the role of ecto-GPR37 as a biomarker should be validated in a larger cohort of patients from different hospitals to confirm its clinical utility, establish its robustness and ensure its applicability as a prognostic tool in disease progression. Ciruela recognizes that “now the next step would be to develop and launch a multicenter clinical project on a European scale that would allow us to carry out the validation study with Parkinson’s patients, necessary to advance towards clinical application”.
On the other hand, researchers, thanks to funding from the Michael J. Fox Foundation, recently adapted a test to determine the presence of ecto-GPR37 in patients’ blood samples, “which makes its analytical determination much simpler”, they conclude.
The study is titled “GPR37 processing in neurodegeneration: a potential marker for the rate of progression of Parkinson’s disease.” And it was published in the academic journal NPJ Parkinson’s Disease. (Source: University of Barcelona)
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Interview Between Time.news Editor and Professor Francisco Ciruela on Parkinson’s Disease Biomarker Discovery
Time.news Editor (TNE): Welcome, Professor Ciruela! Thank you for joining us today to discuss your groundbreaking study on the potential biomarker, ecto-GPR37, for Parkinson’s disease progression. This is exciting news for both the scientific community and patients alike.
Professor Francisco Ciruela (FC): Thank you for having me! It’s a pleasure to discuss our findings.
TNE: Let’s start with the basics. For our readers unfamiliar with the subject, can you explain what ecto-GPR37 is and its significance in the context of Parkinson’s disease?
FC: Certainly! Ecto-GPR37 is a fragment of a protein known as GPR37, which is a type of orphan neuronal G protein-coupled receptor. Our research has shown that increased levels of ecto-GPR37 in cerebrospinal fluid correlate with a slow progression of Parkinson’s disease. This finding is significant because it offers a potential way to stratify patients based on their disease progression, which could lead to more personalized treatment approaches.
TNE: That’s fascinating! You mentioned stratification of patients—why is that so critical in managing Parkinson’s disease?
FC: The progression of Parkinson’s can vary widely among individuals. Patients with rapid progression experience a swift onset of symptoms and generally face a poorer prognosis, including higher risks of cognitive impairment and motor fluctuations. In contrast, those with slower progression maintain functional capacity longer and have milder symptoms initially. By identifying and using biomarkers like ecto-GPR37, clinicians could tailor treatments to better meet the specific needs of each patient.
TNE: Your study involved collaboration across multiple institutions, including global partners. How did this enhance your research?
FC: Collaborative research is vital, especially in complex fields like neurodegenerative diseases. Working with leading institutions from Spain, Sweden, the United States, and the UK allowed us to pool resources, share expertise, and validate our findings across diverse patient populations. This collective approach enhances the reliability of our results and can accelerate the translation of our discoveries into clinical practice.
TNE: Earlier studies indicated ecto-GPR37 might serve as a diagnostic biomarker—what implications does your new finding hold for future research and therapies?
FC: Our latest findings reinforce the notion that ecto-GPR37 may not only aid in diagnosis but also in understanding the progression of the disease. Given that we found elevated levels only in slowly progressive cases, this implies that further exploration of how GPR37 functions could unlock new therapeutic targets. Ultimately, we aim to develop interventions that could potentially slow disease progression or improve patient outcomes.
TNE: That’s encouraging! Moving forward, what do you see as the next steps in your research?
FC: The next steps involve detailed studies to understand the biological mechanisms behind GPR37 processing and its relationship with disease progression. Additionally, we need to explore the pathways associated with ecto-GPR37 to investigate if they can be modulated for therapeutic benefit. Our goal is to provide the medical community with tools that can improve diagnosis and treatment strategies for Parkinson’s patients.
TNE: Thank you, Professor Ciruela. This research is a beacon of hope for many. Any final thoughts you’d like to share?
FC: I want to emphasize the importance of continued investment in research for neurodegenerative diseases. It’s crucial to support scientists who are dedicated to uncovering new insights that can lead to better care and possibly, more effective treatments for Parkinson’s and other related disorders. Together, we can make a difference.
TNE: Thank you once again for sharing your insights, Professor. We look forward to following your future work in this vital area of research!