Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis
Authors' conclusion
RA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti-TNF therapy.
Study context
- Population
- Patients with rheumatoid arthritis (RA) and healthy donors; RA patients starting anti-tumor necrosis factor (anti-TNF) drugs
- Participants
- 253 patients2 cohorts
- Comparison
- RA patients vs healthy donors; NAD+ levels before and after anti-TNF therapy; NAD+ boosters ex vivo
- RAn = 153
- Healthy donorsn = 56reference
- Anti-TNFn = 44
Methodological detailstwo cohorts, proximity extension assay, ex vivo PBMC studies
- Two cohorts
- Proximity extension assay
- Ex vivo PBMC studies
Main finding
As reported in the abstract
- Reduced NAD+ levels in RA samples, with altered activity and expression of genes of NAD+ consumption (sirtuins, PARP, CD38), transport (connexin 43) and biosynthesis (NAMPT, NMNATs)
- Unsupervised clustering identified RA patients with the highest inflammatory profile, lowest NAD+ levels and highest disease activity (DAS28)
- NAD+ levels modulated by anti-TNF therapy in parallel with clinical response
- In peripheral blood mononuclear cells (PBMCs) from RA patients, nicotinamide riboside and nicotinamide increased NAD+ via NAMPT and NMNAT and reduced prooxidative, proapoptotic and proinflammatory status
Original publication
Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis. Arthritis Rheumatol. Published 28 July 2023. doi:10.
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