They found the clinical scores were significantly greater after losmapimod treatment than before (P<.0003). Also, by studying non-responders and responders, they found an elevated C-reactive protein (CRP) level seemed to identify the individuals who responded best to the treatment. They found a significant drop in CRP among these responders, he noted.
“This suggests the amount of systemic inflammation these individuals had before the challenge is related to their decreased initial immune response,” he said.
Dr. Akbar said the findings, once further explored and refined, could mean new therapeutic avenues for older adults with low-grade inflammation.
“If you block inflammation short term, you can increase the memory responses in older people,” he said. “This is going to be relevant for cancer therapy where you short-term-block inflammation. It’s going to be relevant, potentially, for vaccination, where you might be able to block inflammation in the short term in older people to open up a window of opportunity to let their immune systems respond. But these are all questions for the future.”
Cx43 Studied
In another presentation, Marta Varela-Eirin, MS, a PhD student at the Institute of Biomedical Research A Caruña in Spain, discussed work at her lab exploring a way to combat the senescence of chondrocytes, restricting cartilage regeneration and favoring the progress of osteoarthritis.3
They measured levels of the transmembrane channel protein, connexin43 (Cx43), in mesenchymal stem cells and chondrocytes from donors with osteoarthritis, finding the protein acts to regulate the reversion of chondrocytes to a state that is less differentiated.
“Overactivity of Cx43 in the membrane largely maintains this stem-like phenotype,” she said. The findings show that Cx43 is a worthwhile target in OA.
“Cx43 targeting fosters a pro-regenerative environment in OA,” Ms. Varela-Eirin said. “Downregulation of Cx43 promotes cell redifferentiation and is enough to restore the normal chondrocyte phenotype, decreasing senescence and the synthesis of catabolic factors.”
Thomas R. Collins is a freelance writer living in South Florida.
References
- Aguis E, Lacy K, Vukmanovic-Stejic M, et al. Decreased TNF-α synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging. J Exp Med. 2009 Aug 31;206(9):1929–1940.
- Vukmanovic-Stejic M, Chambers ES, Suárez-Fariñas M, et al. Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase-induced inflammation. J Allergy Clin Immunol. 2017 Nov 17. pii: S0091-6749(17)31766-9.
- Varela-Eirin M, Varela-Vazquez A, Paino C, et al. Targeting chondrocyte plasticity via Connexin43 modulation attenuates cellular senescence in osteoarthritis (abstract OP0223). Ann Rheum Dis. 2018 Jun 14;77(suppl):A160.
