Delving into the Latest Updates on AptamiR Therapeutics, Inc. with Synapse

Overview

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Endocrinology and Metabolic Disease

Digestive System Disorders

miRNA

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Endocrinology and Metabolic Disease	1

Top 5 Drug Type	Count

miRNA	1

Top 5 Target	Count

miR-22(microRNA 22)	1

Background:Publications reveal different outcomes achieved by genetically knocking out a long non-coding microRNA-host-gene (lncMIRHG) versus the administration of pharma-cologic antagomirs specifically targeting the guide strand of such intragenic microRNA. This suggests that lncMIRHGs may perform diverse functions unrelated to their role as intragenic miRNA precursors.Objective:This review synthesizes in silico, in vitro, and in vivo findings from our lab and others to compare the effects of knocking out the long non-coding RNA MIR22HG, which hosts miR-22, versus administering pharmacological antagomirs targeting miR-22-3p.Methods:In silico analyses at the gene, pathway, and network levels reveal both distinct and overlapping targets of hsa-miR-22-3p and its host gene, MIR22HG. While pharmacological an-tagomirs targeting miR-22-3p consistently improve various metabolic parameters in cell culture and animal models across multiple studies, genetic knockout of MIR22HG yields inconsistent results among different research groups.Results:Additionally, MIR22HG functions as a circulating endogenous RNA (ceRNA) or "sponge" that simultaneously modulates multiple miRNA-mRNA interactions by competing for binding to several miRNAs.Conclusions:From a therapeutic viewpoint, genetic inactivation of a lncMIRHG and pharmaco-logic antagonism of the guide strand of its related intragenic miRNA produce different results. This should be expected as lncMIRHGs play dual roles, both as lncRNA and as a source for primary miRNA transcripts.

01 Oct 2020·BMJ Open Diabetes Research & CareQ3 · MEDICINE

Metabolic and energetic benefits of microRNA-22 inhibition

Q3 · MEDICINE

ArticleOA

Author: Thibonnier, Marc ; Stocker, Claire ; Esau, Christine ; Wargent, Edward ; Ghosh, Sujoy

IntroductionWe previously demonstrated in primary cultures of human subcutaneous adipocytes and in a mouse model of diet-induced obesity that specific microRNA-22-3p antagomirs produce a significant reduction of fat mass and an improvement of several metabolic parameters. These effects are related to the activation of target genes such asKDM3A,KDM6B,PPARA,PPARGC1BandSIRT1involved in lipid catabolism, thermogenesis, insulin sensitivity and glucose homeostasis.Research design and methodsWe now report a dedicated study exploring over the course of 3 months the metabolic and energetic effects of subcutaneous administration of our first miR-22-3p antagomir drug candidate (APT-110) in adult C57BL/6 male mice. Body composition, various blood parameters and energy expenditure were measured at several timepoints between week 12 and week 27 of age.ResultsWeekly subcutaneous injections of APT-110 for 12 weeks produced a sustained increase of energy expenditure as early as day 11 of treatment, a significant fat mass reduction, but no change of appetite nor physical activity. Insulin sensitivity as well as circulating glucose, cholesterol and leptin were improved. There was a dramatic reduction of liver steatosis after 3 months of active treatment. RNA sequencing revealed an activation of lipid metabolism pathways in a tissue-specific manner.ConclusionsThese original findings suggest that microRNA-22-3p inhibition could lead to a potent treatment of fat accumulation, insulin resistance, and related complex metabolic disorders such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease.

01 Apr 2020·Nucleic Acid TherapeuticsQ3 · MEDICINE

Metabolic Benefits of MicroRNA-22 Inhibition

Q3 · MEDICINE

Article

Author: Esau, Christine ; Thibonnier, Marc

Diabesity is a growing pandemic with substantial health and financial consequences. We are developing microRNA (miRNA)-based drug candidates that transform fat storing adipocytes into fat burning adipocytes (browning effect) to treat metabolic diseases characterized by lipotoxicity. Through phenotypic screening in primary cultures of human subcutaneous adipocytes, we discovered that inhibition of miRNA-22-3p by several complementary antagomirs resulted in increased lipid oxidation, mitochondrial activity, and energy expenditure (EE). These effects may be mediated through activation of target genes like KDM3A, KDM6B, PPARA, PPARGC1B, and SIRT1 involved in lipid catabolism, thermogenesis, and glucose homeostasis. In the model of Diet-Induced Obesity in mice of various ages, weekly subcutaneous injections of various miRNA-22-3p antagomirs produced a significant fat mass reduction, but no change of appetite or body temperature. Insulin sensitivity, as well as circulating glucose and cholesterol levels, was also improved. These original findings suggest that miRNA-22-3p inhibition could become a potent treatment of human obesity and type 2 diabetes mellitus, the so-called diabesity characterized by lipotoxicity and insulin resistance.

100 Deals associated with AptamiR Therapeutics, Inc.

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100 Translational Medicine associated with AptamiR Therapeutics, Inc.

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Pipeline

Pipeline Snapshot as of 26 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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