Ionis Initiates Phase III Trial of Novel Antisense Medicine to Treat Leading Cause of Juvenile-Onset ALS

Ionis Pharmaceuticals, Inc. announced the initiation of a Phase III clinical trial of ION363 in patients with amyotrophic lateral sclerosis (ALS) with mutations in the fused in sarcoma gene.
[Ionis Pharmaceuticals, Inc.]
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PTC Therapeutics Announces the European Approval of Evrysdi for the Treatment of Spinal Muscular Atrophy

PTC Therapeutics, Inc. announced that the European Commission (EC) has granted marketing authorization to Evrysdi for the treatment of spinal muscular atrophy(SMA) in patients 2 months and older. The EC approval was based on two studies; 1) the efficacy results from the FIREFISH study in infants aged 2 to 7 months with symptomatic Type 1 SMA, and 2) the SUNFISH study in children and young adults with Type 2 or 3 SMA.
[PTC Therapeutics, Inc.]
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Exosome-Eluting Stents for Vascular Healing after Ischemic Injury

The authors showed that stents releasing exosomes derived from mesenchymal stem cells in the presence of reactive oxygen species enhance vascular healing in rats with renal ischemia-reperfusion injury, promoting endothelial cell tube formation and proliferation, and impairing the migration of smooth muscle cells.
[Nature Biomedical Engineering]
Hu, S., Li, Z., Shen, D., Zhu, D., Huang, K., Su, T., Dinh, P.-U., Cores, J., & Cheng, K. (2021). Exosome-eluting stents for vascular healing after ischaemic injury. Nature Biomedical Engineering, 1–15. https://doi.org/10.1038/s41551-021-00705-0 Cite
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European Medicines Agency Validates Bristol Myers Squibb’s Application for Opdivo (nivolumab) as Adjuvant Treatment for Patients with Muscle-Invasive Urothelial Carcinoma

Bristol Myers Squibb announced that the European Medicines Agency has validated its type II variation application for Opdivo for the adjuvant treatment of patients with surgically resected, high-risk muscle-invasive urothelial carcinoma.
[Bristol Myers Squibb (BusinessWire, Inc.)]
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Cardiac Macrophages Prevent Sudden Death during Heart Stress

Scientists showed that cardiac macrophages crucially maintained cardiac impulse conduction by facilitating myocardial intercellular communication through gap junctions.
[Nature Communications]
Sugita, J., Fujiu, K., Nakayama, Y., Matsubara, T., Matsuda, J., Oshima, T., Liu, Y., Maru, Y., Hasumi, E., Kojima, T., Seno, H., Asano, K., Ishijima, A., Tomii, N., Yamazaki, M., Kudo, F., Sakuma, I., Nagai, R., Manabe, I., & Komuro, I. (2021). Cardiac macrophages prevent sudden death during heart stress. Nature Communications, 12(1), 1910. https://doi.org/10.1038/s41467-021-22178-0 Cite
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Mitochondrial Aldehyde Dehydrogenase (ALDH2) Rescues Cardiac Contractile Dysfunction in an APP/PS1 Murine Model of Alzheimer’s Disease via Inhibition of ACSL4-Dependent Ferroptosis

In cardiomyocytes isolated from WT mice and in H9C2 myoblasts in vitro, application of Aβ (20 μM) decreased cell survival, compromised cardiomyocyte contractile function, and induced lipid peroxidation; ALDH2 transgene or activator Alda-1 rescued Aβ-induced deteriorating effects.
[Acta Pharmacologica Sinica]
Zhu, Z., Liu, Y., Gong, Y., Jin, W., Topchiy, E., Turdi, S., Gao, Y., Culver, B., Wang, S., Ge, W., Zha, W., Ren, J., Pei, Z., & Qin, X. (2021). Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer’s disease via inhibition of ACSL4-dependent ferroptosis. Acta Pharmacologica Sinica, 1–11. https://doi.org/10.1038/s41401-021-00635-2 Cite
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Generation, Functional Analysis and Applications of Isogenic Three-Dimensional Self-Aggregating Cardiac Microtissues from Human Pluripotent Stem Cells

Scientists describe a protocol to generate cardiomyocytes, cardiac fibroblasts and cardiac endothelial cells, the three principal cell types in the heart, from human induced pluripotent stem cells and combine them in 3D cardiac microtissues.
[Nature Protocols]
Campostrini, G., Meraviglia, V., Giacomelli, E., van Helden, R. W. J., Yiangou, L., Davis, R. P., Bellin, M., Orlova, V. V., & Mummery, C. L. (2021). Generation, functional analysis and applications of isogenic three-dimensional self-aggregating cardiac microtissues from human pluripotent stem cells. Nature Protocols, 1–44. https://doi.org/10.1038/s41596-021-00497-2 Cite
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In Vivo Proximity Labeling Identifies Cardiomyocyte Protein Networks during Zebrafish Heart Regeneration

Researchers applied BioID2 proximity labeling to capture protein networks acting within cardiomyocytes during a key model of innate heart regeneration in zebrafish.
[eLife]
Pronobis, M. I., Zheng, S., Singh, S. P., Goldman, J. A., & Poss, K. D. (2021). In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration. ELife, 10, e66079. https://doi.org/10.7554/eLife.66079 Cite
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The Molecular Basis for Sarcomere Organization in Vertebrate Skeletal Muscle

Investigators determined the molecular architecture of native vertebrate skeletal sarcomeres by electron cryo-tomography.
[Cell]
Wang, Z., Grange, M., Wagner, T., Kho, A. L., Gautel, M., & Raunser, S. (2021). The molecular basis for sarcomere organization in vertebrate skeletal muscle. Cell, 0(0). https://doi.org/10.1016/j.cell.2021.02.047 Cite
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ALDH1A3 Coordinates Metabolism with Gene Regulation in Pulmonary Arterial Hypertension

RNA Sequencing was applied to pulmonary arterial SMC from pulmonary arterial hypertension (PAH) patients with and without a BMPR2 mutation vs. control PASMC to uncover genes required for their heightened proliferation and glycolytic metabolism.
[Circulation]
Li Dan, Shao Ning-Yi, Moonen Jan-Renier, Zhao Zhixin, Shi Minyi, Otsuki Shoichiro, Wang Lingli, Nguyen Tiffany, Yan Elaine, Marciano David P., Contrepois Kévin, Li Caiyun G., Wu Joseph C., Snyder Michael P., & Rabinovitch Marlene. (n.d.). ALDH1A3 Coordinates Metabolism with Gene Regulation in Pulmonary Arterial Hypertension. Circulation, 0(0). https://doi.org/10.1161/CIRCULATIONAHA.120.048845 Cite
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GDF11 Prevents the Formation of Thoracic Aortic Dissection in Mice: Promotion of Contractile Transition of Aortic SMCs

Researchers investigated the expression of GDF11 in thoracic aortic dissection and its effects on aortic smooth muscle cell phenotype transition.
[Journal of Cellular and Molecular Medicine]
Ren, K., Li, B., Liu, Z., Xia, L., Zhai, M., Wei, X., Duan, W., & Yu, S. (n.d.). GDF11 prevents the formation of thoracic aortic dissection in mice: Promotion of contractile transition of aortic SMCs. Journal of Cellular and Molecular Medicine, n/a(n/a). https://doi.org/https://doi.org/10.1111/jcmm.16312 Cite
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