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    New potential drugs for muscle dystrophy found using stem cells

    2+ Channel (SOC) uses induced pluripotent stem cells (iPSC) to Ca in muscular dystrophy myotubes 2+ Adjust the overload. (A) Schematic diagram of a standard re-plating method. iPSCs (DMDΔ44 and DMDΔ44-ctrl) were myogenically predifferentiated in primate ES cell medium (PECM) in the presence of doxycycline and re-differentiated on day 3 in the presence of Y-27632 and 5% doxycycline. It was sown. Knockout serum replacement (KSR) medium. (B) Immunocytochemical analysis of DYS1 and pan-MHC in differentiated myotubes on day 9. Scale bar = 200 µm. (C–F) Relative Ca using DMDΔ44-ctrl and DMDΔ44 cell lines 2+ Concentration, and (D) Ca 2+ Medium, (E) Ca 2+ Channel inhibitors, and (F) SOC inhibitors. * Is p

    Figure 1. Store management Ca2+ Channel (SOC) controls Ca2+ Overloading of muscular dystrophy using induced pluripotent stem cells (iPSC). (A) Schematic diagram of a standard re-plating method. iPSCs (DMDΔ44 and DMDΔ44-ctrl) were myogenically predifferentiated in primate ES cell medium (PECM) in the presence of doxycycline and re-differentiated on day 3 in the presence of Y-27632 and 5% doxycycline. It was sown. Knockout serum replacement (KSR) medium. (B) Immunocytochemical analysis of DYS1 and pan-MHC in differentiated myotubes on day 9. Scale bar = 200 µm. (C–F) Relative Ca2+ Concentrations using DMDΔ44-ctrl and DMDΔ44 cell lines and (D) Ca2+-Free media, (E) Ca2+ Channel inhibitors, and (F) SOC inhibitors. * Indicates p

    Muscular dystrophy, most commonly Duchenne muscular dystrophy (DMD), represents a group of hereditary disorders in which muscles gradually weaken and degenerate. There is no cure for DMD, and most of the drugs available slow the progression and extend the patient’s quality of life. In a new study in biomedicine by Assistant Professor Tomoya Uchimura and Associate Professor Hidetoshi Sakurai, who are participating in T-CiRA in collaboration with Takeda Pharmaceutical Company Limited (Takeda Pharmaceutical Company Limited), a calcium channel operated by a store using iPS cells Shows drugs that act on the muscles that can expand their contractile function. The results reveal that these channels are new drug discovery targets for DMD treatment.

    In addition to being the most common muscular dystrophy, DMD is also the most well-studied. It is characterized by mutations in the protein dystrophin, whose dysfunction or loss causes damage to the muscle as it contracts and relaxes. Eventually, the patient becomes weak and eventually unable to breathe without mechanical ventilation.in the meantime Gene therapy Correcting mutations is the holy grail in DMD treatment research, and drug treatment is believed to be easier to achieve.

    Calcium is good for keeping bones strong. It is also essential for muscles. Muscle contraction depends on a surge in calcium ions released by muscle cells. However, overloading of these ions can be harmful and is generally associated with DMD, Sakurai explains.

    “It is widely accepted that calcium overload regulates the pathogenesis of DMD. It is unclear whether regulating calcium overload has a therapeutic effect,” he said. One of the reasons was the lack of experimental drug compounds, which was one of the reasons Sakurai and Uchimura collaborated with Takeda to access their large drug library.

    After confirming that muscle cells made from iPS cells in DMD patients showed calcium overload, two scientists screened for drugs that interfered with store operations. Calcium channel..

    “Muscle cells have multiple calcium channels, but because they are on the outer cell membrane, the easiest target is the store-operated calcium channel,” Uchimura said.

    They found that some store-operated calcium channel inhibitors block calcium overload and prolong muscle cell contractile function for at least two weeks. In contrast, Muscle cells Without drug treatment, impaired contractile function was seen within a few days.

    Inhibitors specifically blocked certain types of store-operated calcium channels.

    “The STIM1-Orai1 complex is a major store-operated calcium channel,” says Uchimura. “Our results suggest that it is a major regulator of calcium overload in DMD and a potential drug discovery target.”


    iPS cells discover drug discovery targets for muscle diseases


    For more information:
    Tomoya Uchimura et al., Orai1–STIM1 regulates increased Ca2 + recruitment, resulting in a phenotype of contractile Duchenne muscular dystrophy in patient-derived induced pluripotent stem cells. Biomedicine (2021). DOI: 10.3390 / biomedicines9111589

    Provided by
    Kyoto University

    Quote: A new potential drug for muscular dystrophy discovered using stem cells (November 29, 2021) is https: //medicalxpress.com/news/2021-11-potential-drugs-muscle-dystrophy-stem. Obtained from html on November 29, 2021

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    The post New potential drugs for muscle dystrophy found using stem cells appeared first on California News Times.

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