Animal studies confirmed aberrant mRNA splicing in transgenic muscles overexpressing pNO40 which displayed histological features of muscular dystrophy.
In addition, we show that a missense mutation (arginine 440 to glutamine) in WWP1-which is known to cause muscular dystrophy in chickens-increases the ubiquitin ligase-mediated ubiquitination of both β-dystroglycan and WWP1.
The patient iPSC-derived myotubes successfully adopted the skeletal muscle program, as determined by global gene expression profiling, and were functionally responsive to treatment with hypertrophic proteins insulin-like growth factor 1 (IGF-1) and wingless-type MMTV integration site family, member 7A (Wnt7a), which are being investigated as potential treatments for muscular dystrophy in clinical and preclinical studies, respectively.
To determine whether the progression of muscular dystrophy is a consequence of the decline in functional MPCs, we investigated two animal models of DMD: (i) dystrophin-deficient mdx mice, the most commonly utilized model of DMD, which has a relatively mild dystrophic phenotype and (ii) dystrophin/utrophin double knock-out (dKO) mice, which display a similar histopathologic phenotype to DMD patients.
Various dystrophin, utrophin and integrin recombinant cDNAs have been shown to prevent the development of muscular dystrophy in transgenic dystrophic (mdx) mice.
Dystrophin/utrophin double-knockout (dKO) mice develop a more severe and progressive muscular dystrophy than the mdx mice, the most common murine model of Duchenne muscular dystrophy (DMD).
It has been proposed that elevating the levels of utrophin, a close homologue of dystrophin, may act as a therapy for these forms of muscular dystrophy.
Titin is the first urinary biomarker that offers the possibility to develop a simple, non-invasive and easy-to-use test for pre-screening of muscular dystrophies, and may also prove to be useful for the non-invasive follow up of DMD patients under treatment.
In this review, we introduce our recent findings and discuss the current progress in the development of TRPV2 inhibitors and their therapeutic applications for cardiomyopathy associated with muscular dystrophy.
Transient receptor potential cation channel, subfamily V, member 2 (TRPV2) is a principal candidate for abnormal Ca<sup>2+</sup>-entry pathways, which is a potential target for therapy of muscular dystrophy and cardiomyopathy.
We propose that TRPV2 is a principal Ca(2+)-entry route leading to a sustained [Ca(2+)](i) increase and muscle degeneration, and that it is a promising therapeutic target for the treatment of muscular dystrophy.