Parkinson’s disease is the most common neurodegenerative movement disorder. Most cases are of unknown origin, but 10% of patients have genetic mutations that cause the disease to appear. These mutations notably include those affecting the gene that encodes the LRRK2 enzyme, as they are responsible for a large proportion of genetic cases. Therefore, people with alterations in the LRRK2 enzyme have a high risk of developing the disease, but the types of progression biomarkers make it difficult to predict when the first symptoms might appear.
“Our goal was to find biomarkers that help Parkinson’s disease to be diagnosed early, meaning before motor disturbances show up, and non-invasively”, explains Marta Soto, a researcher at the IDIBAPS group Parkinson disease and other neurodegenerative movement disorders: clinical and experimental research. Soto is the lead author of a study published in the journal NPJ Parkinson’s Disease that analyzes levels of microRNAs in the blood serum of asymptomatic carriers of the G2019S mutation of the LRRK2 enzyme.
Despite not presenting symptoms, there is a gradual loss of the neurotransmitter dopamine in the brains of these people, detectable by computerized tomography due to monophoton emission of the dopamine transporter. “This made it possible to classify the patients and study changes in the expression of microRNAs at the different stages of progression”, say Rubén Fernández-Santiago and Mario Ezquerra, also researchers at IDIBAPS and leaders of the study, which enjoyed the participation of the Movement Disorders Unit at Marqués de Valdecilla University Hospital in Santander, headed by Jon Infante.
According to the results, there are specific alterations in carriers with potential as biomarkers. “We have identified four microRNAs: miR-4505, miR-8069, miR-6125 and miR-451a, that can discriminate between carriers of the G2019S mutation of the LRRK2 enzyme with symptoms and those without symptoms”, Soto says. “This finding is significant, as it is the first time that the expression of microRNAs has been analyzed in the pre-motor stages of Parkinson’s and shows their usefulness as indicators in the onset and progression of the disease”.
Exploring the period between the appearance of the first symptoms and the development of the disease is key to finding new mechanisms and treatments. In the specific case of people carrying mutations in the LRRK2 gene, the administration of drugs that inhibit the enzyme is proposed as a therapeutic strategy to be evaluated in clinical trials. This reinforces the need to have biomarkers that allow physicians to follow their patients’ progression.
This study received funding from the Michael J. Fox Foundation for Parkinson’s Research.
Referenced article
Soto M, Fernández M, Bravo P, Lahoz S, Garrido A, Sánchez-Rodríguez A, Rivera-Sánchez M, Sierra M, Melón P, Roig-García A, Naito A, Casey B, Camps J, Tolosa E, Martí MJ, Infante J, Ezquerra M, Fernández-Santiago R. “Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson's disease” in NPJ Parkinson’s Disease 2023 Feb 2;9(1):15. doi: 10.1038/s41531-023-00451-x.