A research team from IDIBELL and the University of Barcelona have identified a potential biomarker of Parkinson’s disease evolution. According to the new study, published in the journal npj Parkinson’s Disease, patients with a slow progression of the disease would have a significant increase in the levels of ecto-GPR37, a molecule found in the cerebrospinal fluid. These results could have important implications for the treatment of patients with this neurodegenerative disease that is characterized by movement disorders such as tremors, rigidity, slowness of movement or postural instability.
“What this study suggests is that this biomarker could be used to define whether the progression of the disease will be rapid or slow. At a clinical level, being able to do this stratification is very important because the management of patients with slow-progressing Parkinson’s disease versus those with rapid progression implies a different clinical approach”, explains the head of the neuropharmacology and pain research group at IDIBELL and the UB, Dr Francisco Ciruela.
According to the researcher, in the case of patients with rapid progression, there is a rapid onset and worsening of symptoms, fluctuations and motor complications, and an increase in the likelihood of cognitive impairment and psychiatric symptoms. On the other hand, patients with slow progression have a gradual onset and progression of symptoms, can maintain higher levels of functional ability and for longer. In addition, they often have milder symptoms, especially in the early stages. “If the disease progresses rapidly, the prognosis is worse than if it progresses slowly, where it can be managed rather as 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 scientist, who has led the research.
Researchers from the Spanish National Cancer Research Centre (CNIO), the Institute for Biomedical Research and Innovation of Cádiz, the Karolinska Institutet (Sweden), the University of California (United States) and King’s College London (United Kingdom) also participated in the study.
Study with samples from patients with different neurodegenerative diseases
This research is a continuation of a 2021 study by the same research team, which found that ecto-GPR37, present in brain neuronal cells, could be a promising candidate for a diagnostic biomarker of Parkinson’s disease. Ecto-GPR37 is a fragment of an orphan neuronal receptor coupled to the G protein called GPR37. Although this receptor is associated with Parkinson’s disease, its neuronal function and endogenous ligand, that is, the specific molecule to which it binds, are not yet known.
In order to validate these 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 systemic atrophy, corticobasal degeneration and progressive supranuclear palsy. “Despite the similarities, patients with these diseases have a different prognosis and do not respond to levodopa, the main treatment for Parkinson’s. Therefore, the exploration of new biomarkers is essential to accurately stratify patients, especially in the early stages, when diagnosis is most challenging,” the researchers explain in the article.
The results of this analysis show that ecto-GPR37 levels only increased in patients with slow-progressing Parkinson’s disease and not in the rapid type or in the rest of the diseases. “This discovery suggests a possible connection between GPR37 processing/expression and the speed of disease progression,” explains Dr Ciruela.
According to the researchers, the most plausible explanation for the presence of ecto-GPR37 in the brain would be the fact that, when the GPR37 receptor reaches the neurons surface, it breaks down and releases ecto-GPR37 to the outside of the cell. As a result of this processing, in this type of slow-progressing 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 have also described a differential pattern of GPR37 processing and expression in the other neurodegenerative diseases analyzed. “This underlines the potential usefulness of GPR37 also to distinguish between different neurodegenerative conditions,” adds Dr. Ciruela.
Multicenter study at European level
Although the results obtained 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 and from different hospitals to confirm its clinical utility, establish its robustness and ensure its applicability as a prognostic tool in the progression of the disease. “Therefore, the next step now would be to develop and launch a multicenter clinical project at European level that allows us to carry out the validation study with Parkinson’s patients, necessary to be able to move towards its clinical application,” stresses Francisco Ciruela.
On the other hand, the researchers have recently adapted, thanks to funding from the Michael J. Fox Foundation, an assay to determine ecto-GPR37 in blood samples from patients, “which greatly facilitates its analytical determination,” they conclude.
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).