Absent or truncated dystrophin in Duchenne (DMD) and Becker (BMD) muscular dystrophies results in impaired vasodilatory pathways and exercise induced muscle ischemia.
Heart failure invariably affects patients with various forms of Muscular Dystrophy (MD), but the onset and molecular sequelae of altered structure and function resulting from full-length dystrophin (Dp427) deficiency in MD heart tissue are poorly understood.To better understand the role of dystrophin in cardiomyocyte development and the earliest phase of DMD cardiomyopathy, we studied human cardiomyocytes differentiated from induced pluripotent stem cells (hiPSC-CMs) obtained from the urine of a Deuchenne Muscular Dystrophy (DMD) patient.
Muscular dystrophy-dystroglycanopathies (MDDG) are a group of genetically heterogeneous autosomal recessive disorders characterized by hypoglycosylation of α-dystroglycan.
Here, we propose the development of a bispecific antibody (biAb) that functions as a surrogate molecular linker to reconnect laminin-211 and the dystroglycan beta-subunit to ameliorate sarcolemmal fragility, a primary pathology in patients with α-dystroglycan-related muscular dystrophies.
Mutations in the gene LMNA cause a wide spectrum of diseases that are now referred to laminopathies, such as muscular dystrophies, cardiomyopathies, and progeroid syndromes.
Cavin-1/PTRF mutations are known to contribute to several human pathologies, including muscular dystrophy and congenital generalized lipodystrophy (CGL).
Ten men (ages 22-42 years; M = 29.3; SD = 7.1) with muscular dystrophy (9 with Duchenne's; 1 with Becker's) completed the Eating Assessment Tool (EAT-10; Ann Otol Rhinol Laryngol 117(12):919-924 [33]) and took part in semi-structured interviews.
In particular, recent gene editing methods that led to the restoration of dystrophin expression in a canine model of muscular dystrophy could be applied to other canine models such as this before translation to humans.
This contribution to the understanding of the structure-function relationship of dystrophin, and especially of the R1-R3 fragment frequently used in the design of protein for gene therapies, should help in the improvement of the strategies for the cure of muscular dystrophies.
Duchenne and Becker muscular dystrophies (DMD/BMD) result in progressive weakness of skeletal and cardiac muscles due to the deficiency of functional dystrophin.
Here, we show that µUtro is a highly functional, non-immunogenic substitute for dystrophin, preventing the most deleterious histological and physiological aspects of muscular dystrophy in small and large animal models.
<b>Results:</b> Totally, 62 mutations of <i>DMD</i> were found in 62 probands with DMD/BMD, and two compound heterozygous mutations in <i>LAMA2</i> were identified in two probands with MDC1A (a type of congenital MD), indicating that the diagnostic yield was 91.4% by MLPA plus NGS for MD diagnosis in this cohort.
These novel approaches may be clinically relevant not only for LGMDR1 but also for other muscular dystrophies with secondary calpainopathy or with abnormal Ca<sup>2+</sup> homeostasis, such as LGMD2B/LGMDR2 or sporadic inclusion body myositis.
Dystroglycan dysfunction in some congenital muscular dystrophies is associated with developmental brain malformations, intellectual disability, and rare epilepsy.
The dystroglycan-matrix interaction is essential for muscle function: disrupted biosynthesis of the matrix-binding modification causes several forms of muscular dystrophy.
Loss of α-dystroglycan-laminin interaction due to defective glycosylation of α-dystroglycan underlies a group of congenital muscular dystrophies often associated with brain malformations, referred to as dystroglycanopathies.