High-content multimodal analysis supports the IL-7/IL-7 receptor axis as a relevant therapeutic target in primary Sjögren's syndrome.

Objective: While the involvement of IL-7/IL-7R axis in pSS has been described in relation to T cells, little is known about the contribution of this pathway in relationship with other immune cells, and its implication in autoimmunity. Using high-content multiomics data, we aimed at characterizing IL-7R expressing cells and the involvement of IL-7/IL-7R pathway in pSS pathophysiology.

Methods: An IL-7 signature established using RNA-sequencing of human PBMCs incubated with IL-7 was applied to 304 pSS patients, and on RNA-Seq datasets from tissue biopsies.

Biomarker-driven development of new therapies for autoimmune diseases: current status and future promises.

Introduction: Auto-immune diseases are complex and heterogeneous. Various types of biomarkers can be used to support precision medicine approaches to autoimmune diseases, ensuring that the right patient receives the most appropriate therapy to improve treatment outcomes.

Areas Covered: We review the recent progress made in modeling several autoimmune diseases such as Systemic Lupus Erythematosus, primary Sjogren Syndrome, and Rheumatoid Arthritis following extensive molecular profiling of large cohorts of patients.

Applications of transcriptomics in support of drug development for osteoarthritis.

Objective: Understanding the heterogeneity and pathophysiology of osteoarthritis (OA) is critical to support the development of tailored disease-modifying treatments. To this aim, transcriptomics tools are highly relevant to delineate dysregulated molecular pathways and identify new therapeutic targets.

Methods: We review the methodology and outcomes of transcriptomics studies conducted in OA, based on a comprehensive literature search of the PubMed and Google Scholar databases using the terms "osteoarthritis", "OA", "knee OA", "hip OA", "genes", "RNA-seq", "microarray", "transcriptomic" and "PCR" as key words.

Industrializing AI-powered drug discovery: lessons learned from the computing platform.

Introduction: As a mid-size international pharmaceutical company, we initiated 4 years ago the launch of a dedicated high-throughput computing platform supporting drug discovery. The platform named ' was built up on the initial predicate to capitalize on our proprietary data while leveraging public data sources in order to foster a Computational Precision Medicine approach with the power of artificial intelligence.

Areas Covered: Specifically, is designed to identify novel therapeutic target candidates.

Model-based computational precision medicine to develop combination therapies for autoimmune diseases.

Introduction: The complex pathophysiology of autoimmune diseases (AIDs) is being progressively deciphered, providing evidence for a multiplicity of pro-inflammatory pathways underlying heterogeneous clinical phenotypes and disease evolution.

Areas Covered: Treatment strategies involving drug combinations are emerging as a preferred option to achieve remission in a vast majority of patients affected by systemic AIDs. The design of appropriate drug combinations can benefit from AID modeling following a comprehensive multi-omics molecular profiling of patients combined with Artificial Intelligence (AI)-powered computational analyses.

Network-based repurposing identifies anti-alarmins as drug candidates to control severe lung inflammation in COVID-19.

While establishing worldwide collective immunity with anti SARS-CoV-2 vaccines, COVID-19 remains a major health issue with dramatic ensuing economic consequences. In the transition, repurposing existing drugs remains the fastest cost-effective approach to alleviate the burden on health services, most particularly by reducing the incidence of the acute respiratory distress syndrome associated with severe COVID-19. We undertook a computational repurposing approach to identify candidate therapeutic drugs to control progression towards severe airways inflammation during COVID-19.

IFN-α: A key therapeutic target for multiple autoimmune rheumatic diseases.

Interferon (IFN)-α has emerged as a major therapeutic target for several autoimmune rheumatic diseases. In this review, we focus on clinical and preclinical advances in anti-IFN-α treatments in systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), systemic sclerosis (SSc), and dermatomyositis (DM), for which a high medical need persists. Promising achievements were obtained following direct IFN-α neutralization, targeting its production through the cytosolic nucleic acid sensor pathways or by blocking its downstream effects through the type I IFN receptor.

A new molecular classification to drive precision treatment strategies in primary Sjögren's syndrome.

There is currently no approved treatment for primary Sjögren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics.