Tracking the relation between neurodegeneration biomarkers in Wilson's disease with neurological phenotypes and prognosis

• Grant number: 24/17919-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2027
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Jacy Bezerra Parmera
• Grantee: Jacy Bezerra Parmera
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Egberto Reis Barbosa ; Fábio Seiji Otsuka ; Igor Vilela Brum ; Izaely Ramos Prates ; Leandro Tavares Lucato ; Pedro Melo Barbosa

Abstract

Introduction: Wilson's disease (WD) is an autosomal recessive hereditary disease that presents a combination of hepatic, neurological, and psychiatric manifestations. In neurological WD, highly variable phenotypes are observed, ranging from mild tremors to debilitating dystonia. Although copper chelators are effective for most patients, a significant proportion develop persistent or progressive neurological symptoms, often with a poor prognosis. The clinical variability and disease course of the neurological form of WD remain poorly understood. In more severe cases, WD may exhibit features of neurodegeneration, such as insidious progression, neuronal loss, and iron accumulation in the basal ganglia, suggesting the involvement of degenerative mechanisms beyond copper toxicity.Objectives: To investigate the relationship between neurodegeneration biomarkers obtained through 7T magnetic resonance imaging (using specific sequences: quantitative susceptibility mapping, neuromelanin, and nigrosome) and optical coherence tomography (retinal nerve fiber layer and macular thinning) with the severity of neurological symptoms in WD.Methods: This prospective observational study involves a cohort of patients with WD followed at the Hospital das Clínicas, University of São Paulo Medical School. The sample will include 30 patients with neurological WD, 15 with non-neurological WD, and 30 age- and sex-matched healthy controls. Participants will undergo serial neurological assessments over a two-year period, using standardized clinical scales, and will be compared based on neurodegeneration biomarkers. (AU)