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Link between Metabolic Stress and Fatigue in Rheumatoid Arthritis. Role of Janus Kinase (JAK) Inhibitors

Ligação do Stresse Metabólico à Fadiga na Artrite Reumatóide. Papel dos Inibidores da Cinase Janus (JAK)

Reference
2024.16799.PEX
Project Start Date
2026-02-01
Project End Date
2027-07-31
Principal Investigator
Scientific Area
Medical and health sciences
Funding Program
Concurso para Projetos de Investigação de caráter Exploratório em Todos os Domínios Científicos 2024

Abstract

Understanding and Treating Fatigue in Rheumatoid Arthritis. Rheumatoid Arthritis (RA) is a chronic autoimmune disease that affects millions of people worldwide. It causes joint pain, stiffness, and swelling, leading to long-term disability and a reduced quality of life. While medical treatments have improved, fatigue remains one of the most common and challenging symptoms of RA, affecting up to 75% of patients. This extreme tiredness goes beyond normal exhaustion, impacting daily activities, work, and emotional well-being. Unfortunately, even when RA symptoms are under control, many people continue to struggle with fatigue, and its causes are not fully understood. Recent research suggests that problems with energy production in cells, specifically within the mitochondria (the “powerhouses” of cells), may play a role in RA-related fatigue. Mitochondria help produce energy, regulate the immune system, and control inflammation. Studies in conditions like fibromyalgia, which also causes severe fatigue and non-inflammatory pain, have shown that mitochondrial dysfunction can lead to low energy levels, suggesting that fatigue may be triggered through mechanisms beyond inflammation. However, its role in RA fatigue remains largely unexplored. A promising class of RA medications, called Janus Kinase inhibitors (JAK inhibitors or JAKi), has been found to significantly reduce fatigue in patients. These drugs work by targeting the immune system, but scientists believe they may also improve how cells produce and use energy. However, we still don’t fully understand how they help fight fatigue. The Goal of This Research. This project aims to uncover the biological reasons behind RA-related fatigue and explore how JAKi improve energy production in cells. By studying immune cells from RA patients, fibromyalgia patients, and healthy individuals, researchers will look for patterns in metabolism (how the body creates and uses energy) and mitochondrial function. The study will use advanced laboratory techniques to analyze how immune cells generate energy, how their mitochondria function, and how these factors relate to inflammation and fatigue. It will also examine how JAKi influence these processes, potentially offering new ways to treat fatigue in RA. Why This Matters. Fatigue is one of the biggest unmet challenges in RA treatment. By better understanding its causes, this research could lead to new and more effective treatments to help people with RA regain their energy and improve their quality of life. This study is led by a team of experts in rheumatology, immunology, and metabolism, working at a leading health unit with access to over 1,400 RA patients and a research center of excellence with international reputation. Their findings could transform how we understand and manage fatigue—not just in RA, but in other chronic diseases as well.

Institutions

Main Institutions

  • Universidade de Coimbra (UC)

Other Institutions

  • Centro Hospitalar e Universitário de Coimbra EPE (CHUC)

Funding 60.000,00 €

Fundação para a Ciência e a Tecnologia (FCT) - Portugal

60.000,00 €