A new biomarker of Parkinson’s disease progression?

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 pathology would have a significant increase in the levels of a molecule called ecto-GPR37 in the cerebrospinal fluid.

What was discovered in this study could have important repercussions for the treatment of patients with this neurodegenerative disease, which is characterized by movement disorders such as tremors, rigidity, slowness of movement or postural instability.

The study was carried out by a team of researchers from the University of Barcelona (UB) and the Bellvitge Biomedical Research Institute (IDIBELL), headed by Josep Argerich from the 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 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, fluctuations and motor complications, as well as an increased probability of cognitive deterioration 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 ability 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, since it can be managed more like a chronic disease. Consequently, in patients with rapid progression, more complex clinical management is required than in those with slow progression, who have a better prognosis,” highlights the UB professor, co-author of the study.

From left to right: Josep Argerich and Francisco Ciruela. (Photo: University of Barcelona. CC BY)

Researchers from the National Cancer Research Center (CNIO) in Spain also participated in the work; the Biomedical Research and Innovation Institute of Cádiz 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 the continuation of a 2021 study by the same research team, which discovered that ecto-GPR37, present 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 G protein-coupled neuronal receptor called GPR37. Although it is a receptor associated with Parkinson’s disease, its neuronal function and endogenous ligand, that is, the specific molecule to which it binds, are not yet known.

To validate the previous results and check 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 neurodegenerative diseases with clinical characteristics similar to Parkinson’s, such as multiple system atrophy, corticobasal degeneration and progressive supranuclear palsy. The researchers detail that, “despite the similarities, patients with 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 diagnosis is more challenging.”

The results of this analysis show that ecto-GPR37 levels only increased in patients with slowly progressive Parkinson’s disease, and not in the rapid typology or in the rest of the pathologies. “This discovery suggests a possible connection between the processing and expression of GPR37 and the speed 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 to the outside of 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, researchers have also described a differential pattern of processing and expression of GPR37 in the other neurodegenerative diseases analyzed. “This underlines the potential usefulness of GPR37 also to distinguish between different neurodegenerative conditions,” adds the UB professor.

Although the results obtained by the UB and IDIBELL team are very promising, the researchers point out 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 usefulness, establish its robustness and guarantee its applicability as a prognostic tool in the progression of the disease. Ciruela recognizes that “now the next step would be to develop and launch a multicenter clinical project on a European scale that allows 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, have recently adapted an assay to determine the presence of ecto-GPR37 in patient blood samples, “which makes its analytical determination much easier,” they conclude. .

The study is titled “GPR37 processing in neurodegeneration: a potential marker for Parkinson’s Disease progression rate.” And it has been published in the academic journal NPJ Parkinson’s Disease. (Source: University of Barcelona)