Rheumatoid arthritis (RA) is a chronic auto-immune disease affecting 18 million people globally as of 2019, with a higher prevalence among women and those over 55 years. It causes inflammation and pain, primarily in the joints, leading to significant physical disabilities and systemic complications affecting the heart, lungs, and nervous system. Despite no cure, early diagnosis and comprehensive management involving medication, rehabilitation, and possibly surgery can control symptoms and improve quality of life [1]. Recent advances in understanding its signaling pathways [2] and molecular and cellular mechanisms have led to innovative therapeutic approaches. These developments pave the way for more effective treatments and, potentially, a cure.
Molecular & Cellular Mechanisms
Research teams studying RA have been diving into how the disease works on a molecular and cellular level. For instance, one study looked at celastrol, a substance known for fighting arthritis, and found it can interfere with calcium balance in cells of the joints, leading to autophagic cell death and less arthritis symptoms [3]. This observation suggests that interfering with calcium in inflammatory cells could be a new way to tackle arthritis. Another important finding is about a protein called Sirtuin 5 (SIRT5), which helps control energy and inflammation in the body [4]. Boosting SIRT5 levels might significantly reduce RA symptoms. There’s also exciting work on a specific gene mutation on p53 tumor suppressor gene (p53R211*) that could help by calming down immune system cells and lowering inflammation, offering a new direction for RA treatments [5]. Researchers are also looking into non-coding RNAs, which could help diagnose RA earlier and predict how well treatments might work, paving the way for more personalized care and treatment [6]. Lastly, a study on how aging affects RA suggested that clearing away the accumulated DNA fragments could be a new preventive approach for disease progression [7]. These discoveries are opening up new paths for understanding and treating RA.
Therapeutic Approaches & Treatment Mechanisms
In the search for new ways to treat rheumatoid arthritis (RA), researchers are exploring innovative therapeutic approaches. Far-infrared radiation (FIR) has emerged as a promising non-drug treatment, successfully reducing inflammation by suppressing the activity of specific genes involved in the disease [8]. Additionally, the combination of epalrestat with an anti-oxidant “N-acetylcysteine (NAC)” addresses the drawbacks of current treatments by mitigating toxicity and inflammation, where epalrestat alone might worsen symptoms by building up harmful substances [9]. There’s also progress in tackling drug resistance, a significant hurdle in RA treatment. Studies have found that mutations in the p53 tumor suppressor gene can make certain arthritis drugs less effective, pointing toward the need for personalized treatment strategies to improve patient outcomes [10].
As we delve into the complexities of RA, it becomes clear that the battle against this debilitating condition is fought on multiple fronts. From unraveling the intricate molecular and cellular mechanisms to exploring innovative therapeutic strategies, the scientific community continues to make significant strides. As research progresses, the hope for those affected by RA grows, promising a future where this chronic condition can be managed more effectively.
*Notes: This article provides research teasers for each reference to showcase the novelties
References
[1] World Health Organization, “Rheumatoid arthritis,” https://www.who.int/news-room/fact-sheets/detail/rheumatoid-arthritis
[2] Q. Ding et al., “Signaling pathways in rheumatoid arthritis: implications for targeted therapy,” Sig Transduct Target Ther, vol. 8, no. 1, p. 68, Feb. 2023, doi: 10.1038/s41392-023-01331-9.
[3] V. K. W. Wong et al., “Ca2+ signalling plays a role in celastrol‐mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in rats,” British J Pharmacology, vol. 176, no. 16, pp. 2922–2944, Aug. 2019, doi: 10.1111/bph.14718.
[4] N. Zhang et al., “Sirtuin 5 deficiency increases disease severity in rats with adjuvant-induced arthritis,” Cell Mol Immunol, vol. 17, no. 11, pp. 1190–1192, Nov. 2020, doi: 10.1038/s41423-020-0380-4.
[5] Y. Zeng et al., “Mutant p53R211* ameliorates inflammatory arthritis in AIA rats via inhibition of TBK1-IRF3 innate immune response,” Inflamm. Res., vol. 72, no. 12, pp. 2199–2219, Dec. 2023, doi: 10.1007/s00011-023-01809-w.
[6] J. Yang et al., “The role of non-coding RNAs (miRNA and lncRNA) in the clinical management of rheumatoid arthritis,” Pharmacological Research, vol. 186, p. 106549, Dec. 2022, doi: 10.1016/j.phrs.2022.106549.
[7] W.-D. Luo et al., “Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis,” Nat Commun, vol. 14, no. 1, p. 4394, Jul. 2023, doi: 10.1038/s41467-023-40113-3.
[8] X. Chen et al., “Far infrared irradiation suppresses experimental arthritis in rats by down-regulation of genes involved inflammatory response and autoimmunity,” Journal of Advanced Research, vol. 38, pp. 107–118, May 2022, doi: 10.1016/j.jare.2021.08.015.
[9] L. Wang et al., “N -Acetylcysteine overcomes epalrestat-mediated increase of toxic 4-hydroxy-2-nonenal and potentiates the anti-arthritic effect of epalrestat in AIA model,” Int. J. Biol. Sci., vol. 19, no. 13, pp. 4082–4102, 2023, doi: 10.7150/ijbs.85028.
[10] C. Qiu et al., “The potential development of drug resistance in rheumatoid arthritis patients identified with p53 mutations,” Genes & Diseases, vol. 10, no. 6, pp. 2252–2255, Nov. 2023, doi: 10.1016/j.gendis.2023.02.007.
Rheumatoid arthritis (RA) is a chronic auto-immune disease affecting 18 million people globally as of 2019, with a higher prevalence among women and those over 55 years. It causes inflammation and pain, primarily in the joints, leading to significant physical disabilities and systemic complications affecting the heart, lungs, and nervous system. Despite no cure, early diagnosis and comprehensive management involving medication, rehabilitation, and possibly surgery can control symptoms and improve quality of life [1]. Recent advances in understanding its signaling pathways [2] and molecular and cellular mechanisms have led to innovative therapeutic approaches. These developments pave the way for more effective treatments and, potentially, a cure.
Molecular & Cellular Mechanisms
Research teams studying RA have been diving into how the disease works on a molecular and cellular level. For instance, one study looked at celastrol, a substance known for fighting arthritis, and found it can interfere with calcium balance in cells of the joints, leading to autophagic cell death and less arthritis symptoms [3]. This observation suggests that interfering with calcium in inflammatory cells could be a new way to tackle arthritis. Another important finding is about a protein called Sirtuin 5 (SIRT5), which helps control energy and inflammation in the body [4]. Boosting SIRT5 levels might significantly reduce RA symptoms. There’s also exciting work on a specific gene mutation on p53 tumor suppressor gene (p53R211*) that could help by calming down immune system cells and lowering inflammation, offering a new direction for RA treatments [5]. Researchers are also looking into non-coding RNAs, which could help diagnose RA earlier and predict how well treatments might work, paving the way for more personalized care and treatment [6]. Lastly, a study on how aging affects RA suggested that clearing away the accumulated DNA fragments could be a new preventive approach for disease progression [7]. These discoveries are opening up new paths for understanding and treating RA.
Therapeutic Approaches & Treatment Mechanisms
In the search for new ways to treat rheumatoid arthritis (RA), researchers are exploring innovative therapeutic approaches. Far-infrared radiation (FIR) has emerged as a promising non-drug treatment, successfully reducing inflammation by suppressing the activity of specific genes involved in the disease [8]. Additionally, the combination of epalrestat with an anti-oxidant “N-acetylcysteine (NAC)” addresses the drawbacks of current treatments by mitigating toxicity and inflammation, where epalrestat alone might worsen symptoms by building up harmful substances [9]. There’s also progress in tackling drug resistance, a significant hurdle in RA treatment. Studies have found that mutations in the p53 tumor suppressor gene can make certain arthritis drugs less effective, pointing toward the need for personalized treatment strategies to improve patient outcomes [10].
As we delve into the complexities of RA, it becomes clear that the battle against this debilitating condition is fought on multiple fronts. From unraveling the intricate molecular and cellular mechanisms to exploring innovative therapeutic strategies, the scientific community continues to make significant strides. As research progresses, the hope for those affected by RA grows, promising a future where this chronic condition can be managed more effectively.
*Notes: This article provides research teasers for each reference to showcase the novelties
References
[1] World Health Organization, “Rheumatoid arthritis,” https://www.who.int/news-room/fact-sheets/detail/rheumatoid-arthritis
[2] Q. Ding et al., “Signaling pathways in rheumatoid arthritis: implications for targeted therapy,” Sig Transduct Target Ther, vol. 8, no. 1, p. 68, Feb. 2023, doi: 10.1038/s41392-023-01331-9.
[3] V. K. W. Wong et al., “Ca2+ signalling plays a role in celastrol‐mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in rats,” British J Pharmacology, vol. 176, no. 16, pp. 2922–2944, Aug. 2019, doi: 10.1111/bph.14718.
[4] N. Zhang et al., “Sirtuin 5 deficiency increases disease severity in rats with adjuvant-induced arthritis,” Cell Mol Immunol, vol. 17, no. 11, pp. 1190–1192, Nov. 2020, doi: 10.1038/s41423-020-0380-4.
[5] Y. Zeng et al., “Mutant p53R211* ameliorates inflammatory arthritis in AIA rats via inhibition of TBK1-IRF3 innate immune response,” Inflamm. Res., vol. 72, no. 12, pp. 2199–2219, Dec. 2023, doi: 10.1007/s00011-023-01809-w.
[6] J. Yang et al., “The role of non-coding RNAs (miRNA and lncRNA) in the clinical management of rheumatoid arthritis,” Pharmacological Research, vol. 186, p. 106549, Dec. 2022, doi: 10.1016/j.phrs.2022.106549.
[7] W.-D. Luo et al., “Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis,” Nat Commun, vol. 14, no. 1, p. 4394, Jul. 2023, doi: 10.1038/s41467-023-40113-3.
[8] X. Chen et al., “Far infrared irradiation suppresses experimental arthritis in rats by down-regulation of genes involved inflammatory response and autoimmunity,” Journal of Advanced Research, vol. 38, pp. 107–118, May 2022, doi: 10.1016/j.jare.2021.08.015.
[9] L. Wang et al., “N -Acetylcysteine overcomes epalrestat-mediated increase of toxic 4-hydroxy-2-nonenal and potentiates the anti-arthritic effect of epalrestat in AIA model,” Int. J. Biol. Sci., vol. 19, no. 13, pp. 4082–4102, 2023, doi: 10.7150/ijbs.85028.
[10] C. Qiu et al., “The potential development of drug resistance in rheumatoid arthritis patients identified with p53 mutations,” Genes & Diseases, vol. 10, no. 6, pp. 2252–2255, Nov. 2023, doi: 10.1016/j.gendis.2023.02.007.
