Plasma microRNA expression in a cohort of patients with spastic hereditary paraplegia type 4 (SPG4)

• Grant number: 25/21786-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2025
• End date: February 28, 2027
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcondes Cavalcante Franca Junior
• Grantee: Karen Mei Chu
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/06739-4 - Searching for causes, biomarkers and therapies for motor neuronopathies/axonopathies, AP.JP2

Abstract

Hereditary Spastic Paraplegia type 4 (SPG4) is the most common form of Hereditary Spastic Paraplegia (HSP), a clinically and genetically heterogeneous group of neurodegenerative diseases. The core feature of HSPs is the degeneration of corticospinal tract axons, which causes progressive weakness and spasticity in the lower limbs. Despite a global incidence of 3.6 cases per 100,000 individuals, there are still no definitive treatments to improve the condition. The absence of objective, sensitive, and non-invasive biomarkers that can be used to monitor disease progression and evaluate response in clinical trials has become an obstacle to the development of new therapies. MicroRNAs (miRNAs) emerge as promising prognostic biomarkers, as they are already being explored in neurological diseases such as Amyotrophic Lateral Sclerosis (ALS) and Friedreich's Ataxia (FA), conditions where the association with miRNAs has already been studied by our group. Therefore, in this project, we will characterize the expression profile of miRNAs in the plasma of patients with SPG4 and compare it with paired controls, so that we can identify abnormally expressed miRNAs in patients and characterize their clinical correlates. The miRNA analysis will be performed using RNAseq, a Next-Generation Sequencing (NGS) technique. The differentially expressed miRNAs will be validated by the RT-qPCR (Reverse Transcription Quantitative PCR) technique. It is expected that the abnormally expressed miRNAs identified in the study may be useful for the stratification and follow-up of patients in future clinical studies. (AU)