Coya Therapeutics, Inc. announced the recent publication of an article entitled “Ex vivo expanded human regulatory T cells modify neuroinflammation in a preclinical model of Alzheimer's Disease” in the peer reviewed journal Acta Neuropathologica Communications. The preclinical study was conducted by Ali Faridar, M.D., of Houston Methodist Hospital (Houston, Texas), under the leadership of Stanley Appel, M.D., the chair of Coya's Scientific Advisory Board. The study investigated the therapeutic effects of ex vivo expanded human Tregs on 5xFAD immunodeficient mice (5xFAD-Rag2KO), a well characterized model of AD.

Treg administration reduced the levels of both soluble and insoluble Aß40 and Aß42 in the dentate gyrus and frontal cortex of treated animals compared to controls. Furthermore, Treg-treated mice showed significant reduction in total and plaque-associated microglia as well as reactive astrocytes in dentate gyrus and frontal cortex versus untreated mice. Consistent with these findings, proteomic evaluation of the neuroinflammation transcriptome revealed that Treg administration down regulated multiple inflammatory pathways that have been observed to be associated with toxic amyloid beta (Aß) including pro-inflammatory cytokines (IL1A&B, IL6), complement cascade (C1qa, C1qb, C4a/b), toll like receptors (Tlr3, Tlr4 and Tlr7) and microglial activations markers (CD14, Tyrobp, Trem2).

The reduction in the number of plaque-associated glial cells and suppression of pro-inflammatory signaling pathways within these cells following Treg therapy may attenuate the contribution of these toxic glial cells in AD pathology resulting in mitigation of amyloid burden.