Montreal Neurological Institute and Hospital

A community-validated tool for clinical outcome calculation in multiple sclerosis: Consensus development and scenario-specific recommendations

Background: Reproducibility and comparability of disability outcomes remain major challenges in multiple sclerosis (MS) research. Definitions of disability progression vary widely across studies, and calculation criteria are often insufficiently documented to enable replication....

PD-1 regulates CD4+ T cell-mediated CD8+ T cell responses in the brain to balance viral control and neuroinflammation

Abstract Programmed cell death protein 1 (PD-1) is expressed by T cells during progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease caused by the human-only JC polyomavirus. Why PD-1 blockade finds variable success in PML patients is unclear. Brain C...

Longitudinal progression, metrics, age-dependence, and modifiers of ataxia severity in SCA27B: a multicentre study of 219 patients

Background Spinocerebellar Ataxia 27B (SCA27B) is a novel, frequent and likely treatable late-onset autosomal-dominant ataxia caused by GAA repeat-expansions in FGF14 . For understanding disease evolution and imminent trial planning, metrics of the most widely used clinical outco...

Triple potentiator combinations increase the functional correction of several CFTR gating mutants

The Trikafta drug combination, comprising the corrector tezacaftor (VX-661), the potentiator ivacaftor (VX-770) and the dual corrector/potentiator elexacaftor (VX-445), has been FDA-approved for treatment of cystic fibrosis caused by ~300 cystic fibrosis transmembrane conductance...

Data-driven mapping of known and novel fluid biomarker progression profiles in genetic frontotemporal lobar degeneration

Abstract Introduction Recent proteomic studies have identified both established and novel proteins in genetic frontotemporal lobar degeneration (FTLD). However, it remains unclear at what point in the disease these proteins deviate from normal levels and how their trajectories re...

Mapping basal ganglia circuitry in altered states of consciousness: from pathology to pharmacology

The precise neuromodulatory mechanisms underlying consciousness and its disorders, despite growing evidence in both animals and humans, remain poorly understood at the subcortical level. The basal ganglia, a key component of the cortico-basal ganglia-thalamo-cortical loop, are kn...