Blog Archives
Development of a checklist for clinical trials in rare disease
Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of … [Read more]
Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes
Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, the authors chose the stem-loop RNA structure TSL2, which overlaps with the 5′ … [Read more]
Institute seminar – June 18th – Giulio Cossu (UK)
Cell-mediated exon skipping for DMD: why it may work Monday 18 June 2018 – 12:00 Giulio Cossu, MD, FMedSci (Constance Thornley Professor of Regenerative Medicine, Division of Cell Matrix Biology & Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester., Manchester Academic Health Science Centre, UK) Host : Gill Butler-Browne Amphi Charcot … [Read more]
Treating dermatomyositis with ruxolitinib
A French team has confirmed the link between the activation of interferon 1 (IFN) and the onset of dermatomyositis, and have demonstrated the efficacy of an interferon 1 inhibitor in 4 people with this disease. People with dermatomyositis have abnormal levels of IFN in the blood and muscles. A link between the activation of IFN … [Read more]
Feasibility and reliability of muscle shear wave elastography in IBM
Degenerative muscle changes may be associated with changes in muscle mechanical properties. Shear wave elastography (SWE) allows direct quantification of muscle shear modulus (MSM). In this study, led by two teams from the Institute of Myology*, the aim was to evaluate the feasibility and reliability of SWE in the severely disordered muscle as observed in … [Read more]
MFN2 agonists reverse mitochondrial defects in preclinical models of CMT2A
Mitofusins (MFNs) promote fusion-mediated mitochondrial content exchange and subcellular trafficking. Mutations in Mfn2 cause neurodegenerative Charcot-Marie-Tooth disease type 2A (CMT2A). In this article, researchers showed that MFN2 activity can be determined by Met376 and His380 interactions with Asp725 and Leu727 and controlled by PINK1 kinase-mediated phosphorylation of adjacent MFN2 Ser378 Small-molecule mimics of the peptide-peptide … [Read more]
Cataract formation in DMD patients on long-term glucocorticoid therapy
The medical records of Duchenne muscular dystrophy (DMD) patients on long-term glucocorticoid therapy (GC) treatment were reviewed retrospectively to evaluate the development of cataracts or ocular hypertension in patients. The main outcome measures were prevalence of cataracts and ocular hypertension, age of first detection of cataract, time from initial steroid use to first detection of … [Read more]
PAX7 target genes are globally repressed in FSH skeletal muscle
Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to hypomethylation of D4Z4 repeats on chromosome 4q causing expression of the DUX4 transcription factor. However, DUX4 is difficult to detect in FSHD muscle biopsies and it is debatable how robust changes in DUX4 target gene expression are as an FSHD biomarker. PAX7 is a … [Read more]
Defining the natural history of dysferlinopathies using muscle MRI
Dysferlinopathies are caused by mutations in the DYSF gene. Previous muscle imaging studies describe a selective pattern of muscle involvement in smaller patient cohorts, but a large imaging study across the entire spectrum of the dysferlinopathies had not been performed and previous imaging findings were not correlated with functional tests.Thisstudypresents cross-sectional T1-weighted muscle MRI … [Read more]
Novel dystrophin expression following long-term treatment with eteplirsen
This study describes the quantification of novel dystrophin production in patients with Duchenne muscular dystrophy (DMD) after long-term treatment with eteplirsen. Clinical study 202 was an observational, open-label extension of the randomized, controlled study 201 assessing the safety and efficacy of eteplirsen in patients with DMD with a confirmed mutation in the DMD gene … [Read more]
