| First Author | Beckmann N | Year | 2017 |
| Journal | Cell Physiol Biochem | Volume | 43 |
| Issue | 4 | Pages | 1460-1471 |
| PubMed ID | 29035882 | Mgi Jnum | J:319291 |
| Mgi Id | MGI:6863568 | Doi | 10.1159/000481968 |
| Citation | Beckmann N, et al. (2017) Regulation of Arthritis Severity by the Acid Sphingomyelinase. Cell Physiol Biochem 43(4):1460-1471 |
| abstractText | BACKGROUND/AIMS: Rheumatoid arthritis is a chronic autoimmune disease hallmarked by inflammation in synovial joints. Treatment is hampered by the lack of a cure and current disease-modifying drugs are associated with potentially severe toxicities. METHODS: We investigated arthritis severity by measuring joint swelling and pro-inflammatory cytokine production in a murine experimental model of inflammatory arthritis (antigen-induced arthritis). We analyzed acid sphingomyelinase knock-out mice and wild-type littermates, as well as mice treated with the pharmacological acid sphingomyelinase inhibitor amitriptyline. RESULTS: Genetic ablation or pharmacological inhibition of acid sphingomyelinase reduced joint swelling and levels of pro-inflammatory cytokines in the arthritic joint. CONCLUSION: We identified acid sphingomyelinase as a novel druggable target in rheumatoid arthritis. Functional inhibitors of acid sphingomyelinase have been clinically used for decades, are well tolerated and suitable for long-term treatment. They would be immediately available for clinical development as a novel rheumatoid arthritis therapy. |
