Generation of two Duchenne muscular dystrophy patient-specific induced pluripotent stem cell lines DMD02 and DMD03 (MUNIi001-A and MUNIi003-A)
Publication date: Available online 9 September 2019Source: Stem Cell ResearchAuthor(s): Jelinkova Sarka, Markova Lenka, Pesl Martin, Valáškova Iveta, Makaturová Eva, Jurikova Lenka, Vondracek Petr, Lacampagne Alain, Dvorak Petr, C. Meli Albano, Rotrekl VladimirAbstractDuchenne muscular dystrophy (DMD) affects 1:3500–5000 newborn boys and manifests with progressive skeletal muscle wasting, respiratory failure and eventual heart failure. Symptoms show different onset from patients' childhood to the second decade of age. We reprogrammed fibroblasts from two independent DMD patients with a complete loss of dystrophin expression, carrying deletions of exons 45–50 and 48–50. The resulting hiPSCs show expression of pluripotency markers (NANOG, OCT4, SSEA4), differentiation capacity into all three germ layers, normal karyotype, genetic identity to the originating parental fibroblasts and the patient-specific dystrophin mutation.
Duchenne muscular dystrophy (DMD) is a genetic, muscle degenerative disorder whose major cause of death is heart failure (HF). We have developed a novel therapy for HF based on the overexpression of small ubiquitin-like modifier type 1 (SUMO1) protein that improves cardiac function by activating sarcoplasmic reticulum Ca2+-ATPase (SERCA2a). This concept has been demonstrated by therapeutic efficacy in both small and large animal models of HF. Calcium overload in cardiac muscle cells has been a major determinant of the DMD cardiopathogenesis, which we hypothesized would be mitigated by targeting SUMO1.
In this study, we investigated whether N106 treatment can improve DMD-associated cardiac dysfunction and muscle damages.
Myotonic dystrophy type 1 (DM1) is the most common adult muscular dystrophy and affects between 1:3.000 and 1:8.000 individuals worldwide. Cardiac involvement is recorded in about 80% of cases.1 The prevalence of cardiac conduction abnormalities and tachyarrhythmias, both atrial and ventricular, are reasonably well described.2 –7 Data regarding the prevalence of left ventricular systolic dysfunction (LVSD) and heart failure (HF) in DM1 patients are few and conflicting.8,9
Background and Aims: Duchenne Muscular Dystrophy (DMD) is a progressive muscle-wasting disease. Besides skeletal muscle degeneration, important sources of morbidity and mortality are dilated cardiomyopathy, arrhythmias and vascular dysfunction. There is substantial evidence that Tenascin C (TN-C) plays role in left ventricular (LV) remodelling and its serum levels are associated with the severity of LV dysfunction in patients with heart failure. Additionally, recent studies demonstrate that endothelial dysfunction may contribute to the progression of dilated cardiomyopathy.
Cardiomyopathies associated with Duchenne (DMD) or Becker (BMD) muscular dystrophy have been historically noted to have poor outcomes in the pediatric population, but studies in the adult population are sparse. Hypothesis: The goal of this study was to determine the rates of ejection fraction (EF) decline and overall survival outcomes in a cohort of adult patients with dystrophinopathic cardiomyopathies on contemporary heart failure therapies.
Authors: Palladino A, Papa AA, Morra S, Russo V, Ergoli M, Rago A, Orsini C, Nigro G, Politano L Abstract Cardiomyopathy associated with dystrophinopathies - Duchenne muscular Dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XL-CM) and cardiomyopathy of Duchenne/Becker (DMD/BMD carriers - is an almost constant manifestation of these neuromuscular disorders and contribute signiﬁcantly to their morbidity and mortality. Dystrophinopathic cardiomyopathy is the result of the dystrophin protein deficiency at the myocardium level, parallel to that occurring at the skeletal muscle level....
(Florida State University) Researchers found that the protein sarcospan can play a major role in combating heart failure in patients with Duchenne muscular dystrophy.
Authors: Komoriyama H, Fukushima A, Takahashi Y, Kinugawa S, Sera F, Ohtani T, Nakamura A, Sakata Y, Anzai T Abstract Becker muscular dystrophy (BMD) carriers are at risk to developing cardiac dysfunction. The prevalence of female BMD carriers remains underestimated, and the disease progression varies. We herein report the case of a young female BMD carrier who developed dilated cardiomyopathy (DCM) and heart failure without any skeletal muscle signs. Her cardiac dysfunction progressed over a mere two months, resulting in the need for left ventricular assist device implantation. Her case demonstrates that progressi...
In this study, we report the age-associated differences between fetal MSC (fMSC) populations and MSCs isolated from elderly donors with respect to their transcriptomes. We successfully reprogrammed fMSCs (55 days post conception) and adult MSC (aMSC; 60-74 years) to iPSCs and, subsequently, generated the corresponding iMSCs. In addition, iMSCs were also derived from ESCs. The iMSCs were similar although not identical to primary MSCs. We unraveled a putative rejuvenation and aging gene expression signature. We show that iMSCs irrespective of donor age and cell type re-acquired a similar secretome to that of th...
We report the case of a 44 year old patient with Steinert disease who showed an early onset ventricular dysfunction refractory to optimal medical and cardiac resincronization therapy, and underwent to successful heart transplantation. At our knowledge, this is the second heart transplantation performed in a patient affected by Steinert disease after the one reported by Conraads et al in 2002. PMID: 30944906 [PubMed - in process]