Delving into the Latest Updates on AGS-500 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Telomerase

Mechanism

Telomerase activators(Telomerase activators)

Therapeutic Areas

Immune System DiseasesEndocrinology and Metabolic DiseaseSkin and Musculoskeletal Diseases

Active Indication

Diabetes Mellitus, Type 1Hair Diseases

Inactive Indication-

Originator Organization

Ben-Gurion University of the Negev

Active Organization

Neuromagen PharmaStartup

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Human Bone Marrow Mesenchymal Stem cells (hMSC) are a promising candidate for cytotherapy. However, the therapeutic potential is limited since the therapy requires ex-vivo cell culturing in which deterioration in cellular viability and aging is observed with time.Telomerase ribonucleoprotein complex re-elongates telomeres and therefore promotes genomic integrity, proliferation and lifespan. Recently we showed that increasing telomerase reverse transcriptase (TERT) expression by novel compound confers resistance from apoptosis induced by oxidative stress. Here we investigated the possibility that a controlled induction of human TERT (hTERT) levels by chemical compounds (AGS-499 and AGS-500) might improve the functionality of hMSC derived from healthy and neurodegenerative diseased individuals. We demonstrate that AGS treatments of hMSC increased telomerase activity and hTERT levels in a time and dose dependent manner. Prolonged treatments with the compounds increased the average telomeres length, without altering population doublings (PD) or inducing chromosomal aberrations. AGS treatments of hMSC protected the cells from apoptosis and DNA damages induced by H2O2, and from the toxicity induced by long term exposure to DMSO. These AGS effects were shown to be mediated by telomerase since they were not observed when TERT was depleted from hMSC or in mouse embryonic stem cells derived from TERT knockout mice. Furthermore, AGS compounds did not alter the functionality of hMSC as examined by their ability to differentiate into various lineages in the presence of the compounds. These results suggest that pharmaceutical increase of telomerase may confer a beneficial therapeutic advantage in regenerative medicine when hMSC therapy is applied.

100 Deals associated with AGS-500

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