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Telomir Pharmaceuticals, USA [02:00PM-02:30PM]
Title: TELOMIR-1 Induces Telomere Extensions in Primary Human Cell Strains
Background: Telomere repeats, (TTAGGG)n, are added to chromosome ends by the enzyme telomerase, but shortened by cell divisions. Telomere shortening is associated with senescence, idiopathic pulmonary fibrosis, and numerous other features, eliciting the quest for telomere modifying compounds. Numerous tobacco-derived alkaloids exhibit anti-inflammatory properties and analgesic effects. These alkaloids have been shown to have activity in cell cycle regulation including binding to DNA and modifying enzyme function; some alkaloids may be responsible for epigenetic modifications leading to changes in gene expression. A structurally modified version of one of these alkaloids, TELOMIR-1, is posited to modulate telomere length.
Aims: To test the effect of TELOMIR-1 on telomere length in 3 human cell lines: MRC-5 fetal lung fibroblasts, human umbilical endothelial cells (HUVEC), and mesenchymal stem cells (MSC).
Methods: First, primary and stem cell strains were treated with TELOMIR-1 for 48 hours. TELOMIR-1 was dissolved in ethanol (ETOH) as a vehicle, and EtOH alone at 1% was the vehicle control. After 48 hours, Alamar Blue assayed the cells for cytotoxicity, or their DNA was extracted and subjected to telomere length qPCR.
Results: Total telomere length was augmented following TELOMIR-1 treatment at 1, 50, 100, and 500 µM, supporting the hypothesis that TELOMIR-1 extends telomere modulation in MRC-5, HUVEC, and MSC cells. Telomere lengthening was seen in passage 3 of HUVEC and MSCs, and through passage 8 of MRC-5 cells. TELOMIR-1 exhibited moderate cytotoxicity at concentrations above 500 µM in HUVEC and MRC-5 cells, and greater cytotoxicity at 1 mM. Major cell loss was observed in the MSC culture treated with EtOH vehicle and TELOMIR-1 compound at 10 µM and above. Conclusion: This in vitro study shows that TELOMIR-1 increases telomere length at concentrations below the cytotoxicity threshold and provides an accurate platform to validate the potency of TELOMIR-1, critical for regulatory submissions.
Danielle R. Baker obtained her Bachelor of Science from Ithaca College (Ithaca, New York) and graduated with a Ph.D. in Molecular and Cellular and Biology and Genetics from Drexel University (Philadelphia, Pennsylvania) in 2021 studying natural transformation in the bacterial pathogen Haemophilus influenzae. Shortly after graduation, Danielle joined Frontage Laboratories, Inc. (Exton, Pennsylvania), a mid-size pharmaceutical CRO specialized in drug discovery and development. At Frontage Laboratories, Inc., Danielle works within the Biologics, Gene, and Cell Therapy division leading projects for the R&D team. Her primary focus is on molecular biology and cell culture, where she thrives on performing laboratory experiments, generating data, and interfacing with her clients. Danielle’s 9+ years of experience allow her to troubleshoot, execute, and deliver quality research and contribute to the field of drug development.