The Characteristics of Protein Profiles in Extracellular Vesicles Derived from ALS Patients' Body Fluids and the Changes Caused by Ropinirole Hydrochloride Treatment ―[...]

September 18, 2024

A research group has conducted comprehensive longitudinal analysis of the protein profiles of extracellular vesicles (EVs) in the blood and cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients who participated in the Ropinirole Hydrochloride Remedy for Amyotrophic Lateral Sclerosis (ROPALS) trial for the drug ropinirole hydrochloride (ROPI). The research team included Professor Hideyuki Okano (now director of the Keio Regenerative Medicine Research Center) and Senior Lecturer Satoru Morimoto (now Associate Professor at the Keio Frontier Research and Education Collaborative Square at Tonomachi) from the Department of Physiology at the Keio University of Medicine; fifth-year Keio medical student Kusuri Kato; and Koji Ueda, Project Leader at the Cancer Precision Medicine Center of the Japanese Foundation for Cancer Research. Their analysis found that the protein composition of EVs from body fluids in sporadic ALS (SALS) patients differs from that of healthy individuals, and that these changes occur in conjunction with the progression of SALS. Moreover, they found that ROPI appeared to suppress these changes. Additionally, research using astrocytes (iPasts) derived from induced pluripotent stem cells (iPSCs) suggested that ROPI might activate the D2R-CRYAB pathway, which suppresses neuroinflammation. Furthermore, researchers identified protein groups that could serve as useful biomarkers for ALS prognosis prediction and diagnosis using machine learning models.

EVs are secreted into bodily fluids like blood and CSF by most kinds of cells and contain proteins and nucleic acids, leading scientists to posit that they are involved in intercellular communication. Scientists also believe that EVs are involved in the pathogenesis of malignant tumors and neurodegenerative diseases, including SALS, pointing to their potential as biomarkers. However, scientists had yet to conduct comprehensive longitudinal analysis of EV protein composition in SALS, or fully grasp the clinically useful biomarkers for prognosis prediction. Moreover, while findings from the ROPALS trial suggested that ROPI suppressed disease, little was understood about the changes it induced in EV protein composition. In this study, collaborators examined the ROPALS trial via reverse translational research (rTR), comprehensively investigating the protein profiles of EVs using samples collected over time from patients to clarify these aspects.

The findings of this study shed light on an element of the pathogenesis of SALS and the mechanisms by which ROPI exerts therapeutic effects, providing important insights into understanding the disease and developing treatment strategies for SALS. Research findings were published in the official international journal of the Japanese Society of Inflammation and Regeneration, Inflammation and Regeneration, at 7:00 PM JST on July 12, 2024.