Article
Medicine, Research & Experimental
Cedric Happi Mbakam, Joel Rousseau, Yaoyao Lu, Anne Bigot, Kamel Mamchaoui, Vincent Mouly, Jacques P. Tremblay
Summary: In this study, researchers used CRISPR-Cas9 prime editing technology to correct a mutation in the DMD gene, resulting in improved editing efficiency and restoration of dystrophin protein expression. Optimization of the reverse transcription template sequence led to a significant increase in the editing percentage of the target nucleotide.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Review
Biochemistry & Molecular Biology
Hasan Mollanoori, Yazdan Rahmati, Bita Hassani, Meysam Havasi Mehr, Shahram Teimourian
Summary: Duchenne muscular dystrophy is a genetic disorder caused by the inability to produce dystrophin protein. Current treatments are supportive rather than curative, but the CRISPR/Cas9 technology has provided new and promising approaches to correcting DMD gene.
Article
Biochemistry & Molecular Biology
Cedric Happi Mbakam, Joel Rousseau, Guillaume Tremblay, Pouire Yameogo, Jacques P. Tremblay
Summary: Prime editing, derived from the CRISPR/Cas9 discovery, allows for the modification of selected nucleotides in a specific gene. It can be used to correct point mutations in the DMD gene.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Shuojun Li, Moqing Du, Jiamin Deng, Guiyun Deng, Jiaying Li, Zhiyong Song, Heyou Han
Summary: The CRISPR/Cas9 gene editing technology provides a promising strategy for Duchenne muscular dystrophy (DMD) therapy. This study introduces biomineralized nanoparticles (Bm-SpRY NPs) as a method for efficient DMD gene editing in vitro and in vivo, with advantages of biocompatibility and high delivery efficiency.
ACTA BIOMATERIALIA
(2022)
Article
Biotechnology & Applied Microbiology
Sina Fatehi, Ryan M. Marks, Matthew J. Rok, Lucie Perillat, Evgueni A. Ivakine, Ronald D. Cohn
Summary: Muscular dystrophies (MDs) are a group of genetic disorders characterized by progressive muscle loss and weakness. CRISPR/Cas9 genome editing has shown promising potential as a therapeutic intervention for MDs, with significant progress made in precision genetic editing techniques. However, challenges such as targeting satellite cells and improving editing efficiency in specific muscle tissues, as well as delivery improvements and immune response, need to be addressed before moving into clinical trials.
HUMAN GENE THERAPY
(2023)
Article
Pharmacology & Pharmacy
Zeren Sun, Dengqiu Xu, Lei Zhao, Xihua Li, Sijia Li, Xiaofei Huang, Chunjie Li, Lixin Sun, Bing Liu, Zhenzhou Jiang, Luyong Zhang
Summary: The study found that fenofibrate can promote the differentiation of myofibers by down-regulating the expression of myostatin protein in myoblasts, significantly improving muscle function and reducing muscle damage in mdx mice, along with anti-inflammatory effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Clinical Neurology
Giulio Gadaleta, Guido Urbano, Chiara Brusa, Rossella D'Alessandro, Enrica Rolle, Ilaria Cavallina, Alessio Mattei, Fulvia Ribolla, Claudia Raineri, Stefano Pidello, Liliana Vercelli, Federica S. Ricci, Tiziana E. Mongini
Summary: The clinical characteristics of adults with DMD include mechanical ventilation, swallowing and nutritional issues, and bone density alterations. Other issues include respiratory infections, gastrointestinal symptoms, metabolic acidosis, psychiatric symptoms, and chronic pain. Patients have a negative perception of their physical health but a more positive assessment of their mental health.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Cell Biology
Elisa Domi, Malvina Hoxha, Emanuela Prendi, Bruno Zappacosta
Summary: Duchenne muscular dystrophy is a muscular disease with no cure, and SIRT1 has been identified as a potential therapeutic target for the condition. Activation of SIRT1 improves muscle function, while its inhibition leads to muscle fragility.
Article
Medicine, Research & Experimental
Eleonora Maino, Daria Wojtal, Sonia L. Evagelou, Aiman Farheen, Tatianna W. Y. Wong, Kyle Lindsay, Ori Scott, Samar Z. Rizvi, Elzbieta Hyatt, Matthew Rok, Shagana Visuvanathan, Amanda Chiodo, Michelle Schneeweiss, Evgueni A. Ivakine, Ronald D. Cohn
Summary: Tandem duplication mutations are increasingly being recognized as a direct cause of rare heritable diseases, but the lack of suitable animal models has hindered research and therapeutic development. A novel mouse model with a multi-exonic tandem duplication in the Dmd gene was successfully corrected using a CRISPR/Cas9 approach, leading to restoration of full-length dystrophin expression and improvements in histopathological and clinical phenotypes. This study highlights the potential of CRISPR/Cas9 as a powerful tool for accurately modeling and treating tandem duplication mutations.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Elena Gargaun, Sestina Falcone, Guilhem Sole, Julien Durigneux, Andoni Urtizberea, Jean Marie Cuisset, Sofia Benkhelifa-Ziyyat, Laura Julien, Anne Boland, Florian Sandron, Vincent Meyer, Jean Francois Deleuze, David Salgado, Jean-Pierre Desvignes, Christophe Beroud, Anatole Chessel, Alexia Blesius, Martin Krahn, Nicolas Levy, France Leturcq, France Pietri-Rouxel
Summary: This study found that long noncoding RNAs play important roles in Duchenne and Becker muscular dystrophy, particularly in regulating myocyte proliferation and differentiation with potential therapeutic implications. The research suggests that lncRNA44s2 may serve as an accelerator in muscle differentiation process and is associated with a favorable clinical phenotype.
Review
Biochemistry & Molecular Biology
Krzysztof Zablocki, Dariusz C. Gorecki
Summary: Muscular dystrophies are inherited neuromuscular diseases that cause progressive disability and can reduce life expectancy. Loss of dystrophin or mutations in sarcoglycan-encoding genes lead to the loss of a-sarcoglycan ecto-ATPase activity, disrupting purinergic signaling and causing chronic inflammation in dystrophic muscles. Over-activation of P2X7 purinoceptors exacerbates pathology in dystrophic muscle cells. Blocking P2X7 receptors has shown promising results in mouse models and should be considered for the treatment of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Craig M. Zaidman, Crystal M. Proud, Craig M. Mcdonald, Kelly J. Lehman, Natalie L. Goedeker, Stefanie Mason, Alexander P. Murphy, Maitea Guridi, Shufang Wang, Carol Reid, Eddie Darton, Christoph Wandel, Sarah Lewis, Jyoti Malhotra, Danielle A. Griffin, Rachael A. Potter, Louise R. Rodino-Klapac, Jerry R. Mendell
Summary: The study ENDEAVOR demonstrated that the commercial process delandistrogene moxeparvovec is safe and effective in improving micro-dystrophin expression in patients with Duchenne muscular dystrophy. After 12 weeks of treatment, significant improvements were observed in micro-dystrophin expression, as well as patient's functional outcomes and quality of life at 1 year.
ANNALS OF NEUROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Prashant Monian, Chikdu Shivalila, Genliang Lu, Mamoru Shimizu, David Boulay, Karley Bussow, Michael Byrne, Adam Bezigian, Arindom Chatterjee, David Chew, Jigar Desai, Frank Favaloro, Jack Godfrey, Andrew Hoss, Naoki Iwamoto, Tomomi Kawamoto, Jayakanthan Kumarasamy, Anthony Lamattina, Amber Lindsey, Fangjun Liu, Richard Looby, Subramanian Marappan, Jake Metterville, Ronelle Murphy, Jeff Rossi, Tom Pu, Bijay Bhattarai, Stephany Standley, Snehlata Tripathi, Hailin Yang, Yuan Yin, Hui Yu, Cong Zhou, Luciano H. Apponi, Pachamuthu Kandasamy, Chandra Vargeese
Summary: The study describes chemically modified oligonucleotides called AIMers that can efficiently and specifically direct RNA-editing enzymes to edit endogenous transcripts. Fully chemically modified AIMers with chimeric backbones showed enhanced potency and editing efficiency compared to uniformly modified AIMers in vitro. In vivo, AIMers targeted to hepatocytes achieved significant editing without off-target effects in non-human primate liver. This study demonstrates the potential of AIMers for therapeutic applications.
NATURE BIOTECHNOLOGY
(2022)
Article
Medicine, General & Internal
Yuta Horikoshi, Norifumi Kuratani, Ken Tateno, Hiroshi Hoshijima, Tina Nakamura, Tsutomu Mieda, Katsushi Doi, Hiroshi Nagasaka
Summary: The use of remimazolam in pediatric patients with DMD undergoing general anesthesia was shown to be safe and effective, with careful monitoring of drug dosages and anesthesia depth being essential during the procedure.
Article
Biochemistry & Molecular Biology
Caroline Merckx, Boel De Paepe
Summary: Taurine plays a crucial role in muscle functioning, and its regulation is altered in Duchenne Muscular Dystrophy. Taurine supplementation has the potential to reduce inflammation and improve muscle strength in patients.
Article
Cardiac & Cardiovascular Systems
Jia Guo, Qinghai Tian, Monika Barth, Wenying Xian, Sandra Ruppenthal, Hans-Joachim Schaefers, Zhifen Chen, Alessandra Moretti, Karl-Ludwig Laugwitz, Peter Lipp
Summary: This study investigated the role of human BIN1 splice variants in the maintenance and regeneration of EC-coupling in rat adult ventricular myocytes and human-induced pluripotent stem cell-derived cardiac myocytes. The results showed that all five human BIN1 splice variants induced de-novo generation of T-tubules in both cell types. Isoforms with the phosphoinositide-binding motif were found to be most potent in maintenance and regeneration of T-tubules and functional EC-coupling in adult rat myocytes, as well as in enhancing calcium handling in hiPS-CMs.
CARDIOVASCULAR RESEARCH
(2022)
Article
Multidisciplinary Sciences
Dena Esfandyari, Bio Maria Gheo Idrissou, Konstantin Hennis, Petros Avramopoulos, Anne Dueck, Ibrahim El-Battrawy, Laurenz Grueter, Melanie Annemarie Meier, Anna Christina Naeger, Deepak Ramanujam, Tatjana Dorn, Thomas Meitinger, Christian Hagl, Hendrik Milting, Martin Borggrefe, Stefanie Fenske, Martin Biel, Andreas Dendorfer, Yassine Sassi, Alessandra Moretti, Stefan Engelhardt
Summary: MicroRNA-365 regulates human cardiac action potential by modulating key cardiac repolarizing channels.
NATURE COMMUNICATIONS
(2022)
Article
Physiology
Luca Sala, Vladislav Leonov, Manuela Mura, Federica Giannetti, Aleksandr Khudiakov, Alessandra Moretti, Lia Crotti, Massimiliano Gnecchi, Peter J. Schwartz
Summary: During the early stages of the COVID-19 pandemic, the use of drug repurposing to find compounds for improving the prognosis of symptomatic patients was common. Hydroxychloroquine (HCQ) was one of the first drugs used for COVID-19 treatment, but its effectiveness is debated and it may cause electrocardiographic abnormalities. By studying human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), researchers found that HCQ had proarrhythmic effects and could potentially distinguish symptomatic from asymptomatic mutation carriers.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Tarik Bozoglu, Seungmin Lee, Tilman Ziegler, Victoria Jurisch, Sanne Maas, Andrea Baehr, Rabea Hinkel, Amelie Hoenig, Anjana Hariharan, Christina Inyeop Kim, Simon Decker, Haider Sami, Tobias Koppara, Ruppert Oellinger, Oliver J. Muller, Derk Frank, Remco Megens, Peter Nelson, Christian Weber, Angelika Schnieke, Markus Sperandio, Gianluca Santamaria, Roland Rad, Alessandra Moretti, Karl-Ludwig Laugwitz, Oliver Soehnlein, Manfred Ogris, Christian Kupatt
Summary: The study demonstrates a method of retargeting adeno-associated viruses (AAVs) to endothelial cells by coating them with second-generation polyamidoamine dendrimers (G2) linked to endothelial-affine peptides (CNN). This approach improves gene transfer efficiency, potentially enabling applications in vascular and atherosclerosis models.
Article
Cardiac & Cardiovascular Systems
S. Engelhardt, S. Dimmeler, C. Heim, C. Baer, T. Boettger, R. Boon, R. P. Brandes, T. Braun, A. Dueck, J. Gagneur, P. Grote, L. M. Holdt, N. Jae, J. Krishnan, C. Kupatt, K. -l. Laugwitz, M. S. Leisegang, L. Maegdefessel, T. Meitinger, A. Moretti, M. Mueller-McNicoll, M. Sattler, A. Schnieke, M. Schulz, H. Schunkert, H. Schwalbe, D. Teupser, T. Thum, C. Weber, I. Wittig, K. Zarnack
Summary: The discovery of regulatory noncoding RNA molecules has revolutionized our understanding of gene expression. These RNA molecules, especially microRNAs, long noncoding RNAs, and circular RNAs, play important roles in the cardiovascular system and have potential for therapeutic applications. However, the complexity of RNA transcripts and the mechanisms of their actions present significant challenges for further research.
Article
Biochemistry & Molecular Biology
Sarah Duin, Shreya Bhandarkar, Susann Lehmann, Elisabeth Kemter, Eckhard Wolf, Michael Gelinsky, Barbara Ludwig, Anja Lode
Summary: The transplantation of pancreatic islets can prevent complications in diabetes patients. 3D bioprinting can encapsulate islets and improve the success rate of transplantation. This study successfully bioprinted neonatal porcine islet-like cell clusters and demonstrated their functionality in vitro.
Article
Nutrition & Dietetics
Rosamaria Lugara, Simone Renner, Eckhard Wolf, Annette Liesegang, Rupert Bruckmaier, Katrin Giller
Summary: Excessive intake of fats and sugars in the Western diet is a major cause of obesity. This study investigated the effects of Western diet and spirulina supplementation on gestating and lactating domestic pigs as a model for metabolic disturbances. The results suggest that domestic pigs have limited suitability as a model for Western diet-induced metabolic impairments, but low-dose spirulina supplementation can partially attenuate the negative effects.
Article
Cell Biology
Fangfang Zhang, Anna B. Meier, Christine M. Poch, Qinghai Tian, Stefan Engelhardt, Daniel Sinnecker, Peter Lipp, Karl-Ludwig Laugwitz, Alessandra Moretti, Tatjana Dorn
Summary: Cardiomyocytes derived from hiPSCs are used as an excellent in vitro model in cardiovascular research, with changes in action potential dynamics being studied using high-throughput optical AP recordings. The study validated a voltage indicator hiPSC line expressing VSFP and established optical AP recordings in different subtypes and environments, expanding possibilities for non-invasive and long-term AP analysis in cardiovascular research and drug discovery.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elena E. E. Wolf, Anne Steglich, Friederike Kessel, Hannah Kroeger, Jan Sradnick, Simone Reichelt-Wurm, Kathrin Eidenschink, Miriam C. C. Banas, Eckhard Wolf, Ruediger Wanke, Florian Gembardt, Vladimir T. T. Todorov
Summary: PLVAP serves as an early marker of glomerular endothelial injury in diabetic kidney disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lillian Garrett, Dietrich Truembach, Nadine Spielmann, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe De Angelis, Sabine M. Hoelter
Summary: Neuropsychiatric diseases represent a significant global disease burden and require innovative approaches for pathogenic understanding, biomarker identification, and therapeutic strategies. The malfunction of the heart/brain axis, particularly through the autonomic nervous system and brain central autonomic network interaction, plays a crucial role in the etiology of these diseases. This inter-relationship offers potential avenues for novel diagnosis and treatment approaches.
Article
Biotechnology & Applied Microbiology
Anna B. Meier, Dorota Zawada, Maria Teresa De Angelis, Laura D. Martens, Gianluca Santamaria, Sophie Zengerle, Monika Nowak-Imialek, Jessica Kornherr, Fangfang Zhang, Qinghai Tian, Cordula M. Wolf, Christian Kupatt, Makoto Sahara, Peter Lipp, Fabian J. Theis, Julien Gagneur, Alexander Goedel, Karl-Ludwig Laugwitz, Tatjana Dorn, Alessandra Moretti
Summary: The lineage of human epicardium was studied through time course single-cell analysis of epicardioids. The mesothelial envelope of the vertebrate heart, known as the epicardium, serves as the source of multiple cardiac cell lineages during embryonic development and is essential for myocardial growth and repair. Using self-organizing human pluripotent stem cell-derived epicardioids, researchers were able to observe the morphological, molecular, and functional patterning of the epicardium and myocardium, similar to the left ventricular wall. This study provides insights into the specification and differentiation process of different cell lineages in epicardioids, as well as the functional cross-talk between different cardiac cell types.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Dorota Zawada, Jessica Kornherr, Anna B. B. Meier, Gianluca Santamaria, Tatjana Dorn, Monika Nowak-Imialek, Daniel Ortmann, Fangfang Zhang, Mark Lachmann, Martina Dressen, Mariaestela Ortiz, Victoria L. L. Mascetti, Stephen C. C. Harmer, Muriel Nobles, Andrew Tinker, Maria Teresa De Angelis, Roger A. A. Pedersen, Phillip Grote, Karl-Ludwig Laugwitz, Alessandra Moretti, Alexander Goedel
Summary: Cardiogenesis depends on the coordination of multiple progenitor populations. Modulating retinoic acid signaling instructs human pluripotent stem cells to form heart field-specific progenitors with distinct fate potentials, which can be used for studying human cardiac development and disease. Dysregulation in specific transcriptional profiles of heart field progenitors derived from stem cells of patients with hypoplastic left heart syndrome suggests the suitability of the in vitro differentiation platform for disease modeling.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Valerie Pauly, Julia Vlcek, Zhihao Zhang, Nora Hesse, Ruibing Xia, Julia Bauer, Simone Loy, Sarah Schneider, Simone Renner, Eckhard Wolf, Stefan Kaeaeb, Dominik Schuettler, Philipp Tomsits, Sebastian Clauss
Summary: Atrial fibrillation (AF) is a common arrhythmia caused by myocardial ischemia/infarction (MI). Men have a higher prevalence of AF, while women have a higher risk of new onset AF after MI. The impact of sex on AF pathophysiology is largely unknown. In pigs with/without ischemic heart failure (IHF), both male and female pigs showed increased vulnerability to AF. Male pigs had more and longer AF episodes, while female pigs had sinus node dysfunction.
Article
Biochemistry & Molecular Biology
Marie-Christin Schilloks, Isabella-Maria Giese, Arne Hinrichs, Lucia Korbonits, Stefanie M. Hauck, Eckhard Wolf, Cornelia A. Deeg
Summary: This study investigated the effects of impaired GHR signaling on immune functions and immunometabolism in GHR-KO pigs. The results showed significant differences in the relative proportion of the CD4(+)CD8a(-) subpopulation and IFN-a levels between GHR-KO pigs and WT controls. However, no significant difference was found in the respiratory capacity and the capacity for polyclonal stimulation in PBMCs between the two groups. Proteome analysis revealed multiple significant protein abundance differences related to amino acid metabolism, beta-oxidation of fatty acids, insulin secretion signaling, and oxidative phosphorylation between GHR-KO pigs and WT pigs.
Meeting Abstract
Physiology
J. Guo, Q. Tian, M. Barth, W. Xian, S. Ruppenthal, H. -J. Schaefers, Z. Chen, A. Moretti, K. -L. Laugwitz, P. Lipp