Biomarkers in Progressive Supranuclear Palsy

• Grant number: 24/10405-2
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2027
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Egberto Reis Barbosa
• Grantee: Egberto Reis Barbosa
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Artur Martins Novaes Coutinho ; Carlos Alberto Buchpiguel ; Ellison Fernando Cardoso ; Hélio Rodrigues Gomes ; Marcos Castello Barbosa de Oliveira

Abstract

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder pathologically defined by abnormal phosphorylated tau protein (4R) aggregates, with the typical finding of tufted astrocytes. It classically presents as a symmetric, poorly responsive parkinsonism associated with early falls, supranuclear palsy of vertical gaze, dysarthria, dysphagia and cognitive and behavioral symptoms. Several biomarkers have been proposed to be used for diagnosis and follow-up of PSP, but to date none is considered sufficiently reliable for use in clinical practice. With the advent of medications that potentially modify the disease course, it is ever more important to study biomarkers that predict the disease progression, so they can be used as surrogate endpoints in clinical trials. The neurofilament light (NfL) protein appears to be a good candidate to this end. Objectives: To evaluate the clinical data of a cohort of PSP patients, specially disease severity and time to development of predefined milestones, and assess their association with NfL levels in the cerebrospinal fluid (CSF) and blood, aiming to determine if NfL is a reliable biomarker to be used as surrogate endpoint in clinical trials of disease modifying treatments. As secondary objectives, we will assess the clinical profile and compare with imaging exams (magnetic resonance imaging and FDG-PET of the brain). Methods: The cohort will be composed of patients diagnosed as possible and probable PSP, recruited from the movement disorders clinic of Hospital das Clinicas - Medical School - University of Sao Paulo. The volunteers will be assessed with complete neurological evaluation and rating scales, including the PSP rating scale (PSPRS), and will be invited to undergo blood and CSF tests, magnetic resonance imaging and FDG-PET of the brain. The association between time to development of milestones and NfL levels will be statistically assessed through survival analysis. (AU)