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MOLECULAR MECHANISMS OF REDOX REGULATION IN INFLAMMATION

Updated: May 22

We are hopeful that TVALA will reduce p53 expression in people with ALS. There are two recent publications that give us hope. The first paper is by Maor-Nof et. al. (2022), found in Cell. The found that p53 ablation protects neurons from axonal degeneration and cell death caused by C90rf72 expansion. Further, p53 ablation extends the lifespan in a mouse model of C9orf72. The literature references p53 as a driver of ALS in both familial and sporadic ALS. Reducing p53 protein that is involved in apoptosis would be a therapeutic ALS target.


A second paper in Molecular Biology (2023) authored by Novoselova et. al. investigated the thymic hormone thymosin-1a showing that it reduces the pro-inflammatory response of macrophage (RAW 264.7) cells induced by endotoxin. Their results are exciting because they show this pro-molecule of thymopentin significantly reduced the p53 levels and reduced the activity of the p53 gene.


Our work with TVALA is based on the hypothesis that targeting inflammation using a molecule that has multiple normalizing effects (it only regulates dysregulated systems) will slow the progress of ALS in people. TVALA was designed to bind thymopentin receptors. WE investigated thymosin 1a and thymopentin in ALS mouse models and in vitro using multiple cell types including those from ALS patients and compared the results to TVALA. NDR found that TVALA was superior to thymopentin and the longer half-life and CNS penetration could be a better molecule to normalize the inflammation found in ALS. We are enrolling the patients into the first-in-human trials now!


We are continuing to elucidate the effects of TVALA and currently have experiments with Hesperos Inc. using their human-on-a-chip system. So far things are encouraging!









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