Myotonic Dystrophy Type 1 Drug Development: A Pipeline Toward the Market

Overview

Journal Drug Discov Today

Specialty Pharmacology

Date 2021 Apr 2

PMID 33798646

Citations 23

Authors

Marta Pascual-Gilabert

Arturo Lopez-Castel

Ruben Artero

Affiliations

Soon will be listed here.

Abstract

Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular genetic disease with an estimated prevalence of approximately at least half a million individuals based on its vast ethnic variation. Building upon a well-known physiopathology and several proof-of-concept therapeutic approaches, herein we compile a comprehensive overview of the most recent drug development programs under preclinical and clinical evaluation. Specifically, close to two dozen drug developments, eight of which are already in clinical trials, explore a diversity of new chemical entities, drug repurposing, oligonucleotide, and gene therapy-based approaches. Of these, repurposing of tideglusib, mexiletine, or metformin appear to be therapies with the most potential to receive marketing authorization for DM1.

Citing Articles

A Novel Class of FKBP12 Ligands Rescues Premature Aging Phenotypes Associated with Myotonic Dystrophy Type 1.

Garcia-Puga M, Gerenu G, Bargiela A, Espinosa-Espinosa J, Mosqueira-Martin L, Sagartzazu-Aizpurua M Cells. 2024; 13(23).

PMID: 39682688 PMC: 11639790. DOI: 10.3390/cells13231939.

Identification of an RNA-binding perturbing characteristic for thiopurine drugs and their derivatives to disrupt CELF1-RNA interaction.

Tan Y, Zhao Z, Han Q, Xu P, Shen X, Jiang Y Nucleic Acids Res. 2024; 52(18):10810-10822.

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A cyclic pyrrole-imidazole polyamide reduces pathogenic RNA in CAG/CTG triplet repeat neurological disease models.

Ikenoshita S, Matsuo K, Yabuki Y, Kawakubo K, Asamitsu S, Hori K J Clin Invest. 2023; 133(22).

PMID: 37707954 PMC: 10645379. DOI: 10.1172/JCI164792.

Clearance of defective muscle stem cells by senolytics restores myogenesis in myotonic dystrophy type 1.

Conte T, Duran-Bishop G, Orfi Z, Mokhtari I, Deprez A, Cote I Nat Commun. 2023; 14(1):4033.

PMID: 37468473 PMC: 10356779. DOI: 10.1038/s41467-023-39663-3.

All roads lead to cure: Diversity of oligonucleotides in DM1 therapy.

Fiszer A Mol Ther Nucleic Acids. 2023; 32:898-899.

PMID: 37287495 PMC: 10242478. DOI: 10.1016/j.omtn.2023.05.012.

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