Parkinson’s disease is a progressive neurological condition that affects movement, speech, and mobility. Caused by the loss of dopamine-producing neurons critical for motor control, Parkinson’s typically develops over time and can cause additional symptoms, including chronic pain and sleep disturbances.
Parkinson’s disease is a major global health challenge. With prevalence doubling over the past 25 years, more than 8.5 million people worldwide live with the condition, including approximately 30,000 patients in Chile.
At the University of Santiago de Chile (Usach), doctoral candidate Francisco Leiva is investigating the molecular roots of the disease. Based in the Laboratory of Genomics, Molecular Ecology, and Evolutionary Studies, Leiva's research focuses on epitranscriptomics—the study of functional modifications to RNA.
By revealing how RNA modifications influence the causes and symptoms of Parkinson's disease, this cutting-edge research aims to enable early detection and advance the development of potential preventive or curative treatments.
Blood as a Window into the Disease
While most Parkinson’s research focuses directly on the brain, Francisco Leiva and his team took a more accessible approach: analyzing blood samples. Compared to obtaining brain tissue or invasive cerebrospinal fluid, blood tests offer a less invasive and far more practical way to study patients and track disease markers.
“This decision is based on evidence of a possible link between changes in the blood and processes occurring in the nervous system, partly because alterations in the blood-brain barrier have been reported in patients with Parkinson’s,” explained Francisco Leiva.
Using an international database of more than 10,000 Latin American patients—compiled with the help of the U.S. National Institutes of Health, the Michael J. Fox Foundation, and Parkinson Biomarkers—the researchers conducted an epitranscriptomic study that identified 237 genes that differed between patients and controls. Following analysis, 12 key genes related to the disease were identified.
Francisco Leiva emphasizes: “The significance of these genes lies in the fact that they exhibit RNA methylation, a chemical modification that can alter the way a cell reads and uses a genetic message. After reviewing specialized databases, we confirmed that all 12 genes showed alterations in this mark, which reinforces their potential link to Parkinson’s.”
In other words, these chemical marks on RNA suggest that gene regulation is disrupted in Parkinson’s patients. This discovery opens a promising new avenue for understanding the disease's earliest stages and unlocking the cellular mechanisms that drive its onset.
What does this mean for Parkinson’s research?
The ultimate goal of Parkinson’s disease research is to find a cure and reduce patient suffering. For Francisco Leiva, this study is only the beginning. His discovery of RNA modifications in Latin American patients opens a crucial pathway for future research aimed at early diagnosis and targeted therapies.
“I see, both in the paper and in the thesis, that epitranscriptomics—that is, the set of chemical modifications that regulate RNA without changing the genetic sequence—is not only involved but is likely a fundamental part of the process. In fact, modulating these mechanisms could help delay the disease or, in the longer term, prevent it.”
Furthermore, he is certain that the study of transcriptome modifications—the marks that alter how RNA functions—opens the door to a completely unknown and, therefore, little-researched field.
“My goal is to find a cure for this disease or halt its progression; that is my guiding principle. Through my contribution—in this case, from the field of genomics,” concludes Francisco Leiva.
Key collaborators on the Parkinson’s study included researchers from the Neurobiology Laboratory (directed by Dr. Luis Constandil), the Neuroscience Laboratory (directed by Dr. Bernardo Morales), Usach School of Medicine professor Dr. Pedro Chana-Cuevas, and Dr. René Vidal of Universidad Mayor.
For further information, read the full paper Integrating Weighted Gene Co-Expression Network and Differential Expression Analyses to Unveil the Role of RNA m6A Methylation Regulators in Idiopathic Parkinson’s Disease in Latin America.