Dados do Trabalho

Título

Heterogeneous phenotypes of inflammatory demyelinating diseases and TGF-B1 as potential biomarker of disease progression.

Resumo

Idiopathic inflammatory demyelinating diseases (IIDDs) are a group of Central Nervous System disorders which have white matter lesions as common feature. Neuroimaging and molecular assays led to the establishment of more discernible diagnosis in this field, such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and MOG associated diseases (MOGAD), each with their own clinical course and therapeutic interventions. In this work, we aim to determine the clinical profile and disease course in a population of patients from an IIDDs reference center. To explore new tools for course evaluation, we used in vitro assays to propose potential markers.
In preliminary analysis, we had 60 patients enrolled. From those, 46 patients were diagnosed with MS, being 43 with relapse-remitting (RRMS), 2 with secondary progressive disease (SPMS) and 1 with primary progressive (PPMS). 8 presented with NMOSD, 1 with optic neuritis, 1 with acute disseminated encephalomyelitis and 3 with a clinically isolated syndrome. Another patient was still with diagnosis pending. We determined 59,7% of patients presented with a multifocal disease as early as clinical onset, with sensitive (44,%), pyiramidal (30,4%) and brainstem (23,2%) being the most committed functional systems. And although 60% of patients got an EDSS equal or higher than 3,0 during onset, 77,8% got total remission, even if 35,2% didn´t get any medical care. At time of current assessment, though, 25% percent already got to that level. From these, 6 (10% from total) were equal or higher than 6,0.
Investigating which CNS molecules could be used for disease evaluation on those patients, we performed in vitro assays: astrocytes from healthy mice, cells linked to inflammation and synaptic regulation, were cultured and treated with myelin proteins. While MOG exerted little response on those cells,  24 hour treatment of cultures with Nogo-A led to defective expression of pro-synaptogenic factors. Among them, we found a nearly 30% reduction in TGF-B1, a cytokine that in CNS exerts a neuroprotector effect, being currently considered both as therapeutic target and biomarker for an array of neurodegenerative diseases.
Thus, here we identified TGF-B1 as a player in demyelination synaptopathy, with potential for investigation as a biomarker in IIDDs. New assays are still needed to functionally relate that molecule to different stages of disease progression, helping to better define its clinical employability.

Palavras Chave

Demyelination; IIDD; TGF-B1; biomarker discovery