Targeting Myotonic Dystrophy Type 1 with Metformin

García-Puga, Mikel; Saenz-Antoñanzas, Ander; Matheu, Ander; Munain, Adolfo López de

doi:10.3390/ijms23052901

Cited by 16 publications

(15 citation statements)

References 130 publications

(188 reference statements)

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“…This target seems to be involved in both DM1 and DM2 pathogeneses because both DM1 and DM2 are characterized by insulin resistance and predisposition to type 2 diabetes (T2D) [ 3 , 4 , 5 , 6 ]. It was shown that an anti-diabetic drug, metformin, corrects abnormal IR splicing in DM1 mesodermal precursor cells (MPCs) and in DM1 myoblasts ([ 78 ] and reviewed in [ 79 ]). Interestingly, in addition to IR, metformin also improves splicing of other genes, including TNNT2 and Clcn1 [ 78 ].…”

Section: Therapeutic Targets In Dm1 and Dm2mentioning

confidence: 99%

Development of Therapeutic Approaches for Myotonic Dystrophies Type 1 and Type 2

Timchenko

2022

IJMS

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Myotonic Dystrophies type 1 (DM1) and type 2 (DM2) are complex multisystem diseases without disease-based therapies. These disorders are caused by the expansions of unstable CTG (DM1) and CCTG (DM2) repeats outside of the coding regions of the disease genes: DMPK in DM1 and CNBP in DM2. Multiple clinical and molecular studies provided a consensus for DM1 pathogenesis, showing that the molecular pathophysiology of DM1 is associated with the toxicity of RNA CUG repeats, which cause multiple disturbances in RNA metabolism in patients’ cells. As a result, splicing, translation, RNA stability and transcription of multiple genes are misregulated in DM1 cells. While mutant CCUG repeats are the main cause of DM2, additional factors might play a role in DM2 pathogenesis. This review describes current progress in the translation of mechanistic knowledge in DM1 and DM2 to clinical trials, with a focus on the development of disease-specific therapies for patients with adult forms of DM1 and congenital DM1 (CDM1).

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Section: Therapeutic Targets In Dm1 and Dm2mentioning

confidence: 99%

Development of Therapeutic Approaches for Myotonic Dystrophies Type 1 and Type 2

Timchenko

2022

IJMS

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“…However, there is still a long way to go from animal experiments to human experiments to final clinical applications. Also, some studies reveal the efﬁcacy of metformin delaying and/or limiting DM1, not only in diabetes, but also in additional characteristics of its pathobiology[ 26 ]. Besides, in our opinion, regular follow-up to assess lung function, oxygen saturation, ECG, and cardiac function is also critical.…”

Section: Discussionmentioning

confidence: 99%

Myotonic dystrophy type 1 presenting with dyspnea: A case report

Jia¹,

Dong²,

Xue³

et al. 2022

WJCC

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BACKGROUND Myotonic dystrophy type 1 (DM1) is a genetic neuromuscular disease involving multiple systems, especially the cardiopulmonary system. The clinical phenotype of DM1 patients is highly variable, which limits early diagnosis and treatment. In the present study, we reported a 35-year-old female DM1 patient with dyspnea as the primary onset clinical manifestation, analyzed her family's medical history, and reviewed related literature. CASE SUMMARY A 35-year-old woman was admitted to the hospital with dyspnea of 1 mo duration, and sleep apnea for 3 d. Her respiratory pattern and effort were normal, but limb muscle tension was low. Investigation into the patient's medical history revealed that she might have hereditary neuromuscular disease. Electromyography showed that her myotonia potentials were visible in the resting state of the examined muscles, with decreased motor unit potential time limit and amplitude. Genetic testing for DM1 revealed that the cytosine-thymine-guanine (CTG) repeat number of the DMPK gene exceeded 50, while cytosine-CTG expansion in intron 1 of ZNF9 gene was < 30 repeats. The patient was diagnosed with DM1. CONCLUSION DM1 is a genetic neuromuscular disease involving multiple systems, and the clinical phenotype in DM1 is extremely variable. Some patients with DM1 may be presented at the respiratory department because of dyspnea, which should be cautioned by the pulmonologists. There may be no obvious or specific symptoms in the early stage of disease, and clinicians should improve their understanding of DM1 and make an early diagnosis, which will improve patients’ quality of life.

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“… Therapeutic approaches for DM1 discussed in the reviews in the Special Issues of the journal. They include the CRISPR/Cas approach [ 5 , 6 ], as well as the application of small molecules, restoring MBNL1 and CUGBP1 activities or correcting splicing via other RNA-binding proteins [ 7 , 8 , 9 , 10 ]. Although indirectly, several review papers referred to the use of AONs as a potential therapy for DM1 [ 5 , 7 , 8 , 10 , 11 , 12 ].…”

Section: Figurementioning

confidence: 99%

“…MicroRNAs altered in DM1 could also be used as biomarkers. The review by Dr. Munain’s group describes the recent data related to the potential role of small-molecule metformin for the treatment of DM1 [ 8 ]. Some studies showed that metformin improves the splicing of insulin receptors, misregulated in DM1.…”

mentioning

confidence: 99%