Blog Archives
Gene replacement therapy after neuropathy onset provides therapeutic benefit in a model of CMT1X
X-linked Charcot-Marie-Tooth disease (CMT1X), one of the commonest forms of inherited demyelinating neuropathy, results from GJB1 gene mutations causing loss of function of the gap junction protein connexin32 (Cx32). The aim of this study was to examine whether delayed gene replacement therapy after the onset of peripheral neuropathy can provide a therapeutic benefit in the … [Read more]
Gene therapy for Pompe disease: the time is now
Pompe disease (PD) is caused by the deficiency of the lysosomal enzyme acid α-glucosidase (GAA), resulting in systemic pathological glycogen accumulation. PD can present with cardiac, skeletal muscle, and central nervous system manifestations, as a continuum of phenotypes among two main forms: classical infantile-onset PD (IOPD) and late-onset PD (LOPD). IOPD is caused by severe … [Read more]
Emery-Dreifuss muscular dystrophy: focal point nuclear envelope
Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in EMD encoding emerin and LMNA encoding A-type lamins, proteins of the nuclear envelope. In the past decade, there has been an extraordinary burst of research on the nuclear envelope. Discoveries resulting from this basic research have implications for better understanding the pathogenesis and developing treatments for … [Read more]
Gene Therapy for ALS – A Perspective
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease (MND) with no cure. Recent advances in gene therapy open a new perspective to treat this disorder-particularly for the characterized genetic forms. Gene therapy approaches, involving the delivery of antisense oligonucleotides into the central nervous system (CNS) are being tested in clinical trials for patients … [Read more]
Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice
Antisense oligonucleotides (ASOs) targeting pathologic RNAs have shown promising therapeutic corrections for many genetic diseases including myotonic dystrophy (DM1). Thus, ASO strategies for DM1 can abolish the toxic RNA gain-of-function mechanism caused by nuclear-retained mutant transcripts containing CUG expansions (CUGexp). However, systemic use of ASOs for this muscular disease remains challenging due to poor drug … [Read more]
Novel mutation in TNPO3 causes congenital limb-girdle myopathy with slow progression
The authors report a second family with autosomal dominant transportinopathy presenting with congenital or early-onset myopathy and slow progression, causing proximal and less pronounced distal muscle weakness. Patients had clinical examinations, muscle MRI, EMG, and muscle biopsy studies. The MYOcap gene panel was used to identify the gene defect in the family. Muscle biopsies were … [Read more]
A new family with transportinopathy: increased clinical heterogeneity
The authors describe a family with a novel TNPO3 mutation of limb-girdle muscular dystrophy D2 (or LGMD 1F), a rare muscle disorder with autosomal dominant inheritance, first identified in an Italo-Spanish family where the causative defect has been found to be due to TNPO3 gene mutation, encoding transportin-3 protein (TNPO3). They present the clinical, histopathological … [Read more]
Robust and accurate detection and sizing of repeats within the DMPK gene using a novel TP-PCR test
Myotonic dystrophy type 1 is a multisystem disorder caused by the expansion of a trinucleotide repeat in the DMPK gene. In this study the researchers evaluated the performance of the FastDM1TM DMPK sizing kit in myotonic dystrophy type 1 testing. This commercially available triplet repeat-primed PCR based kit was validated using reference and clinical samples. … [Read more]
Institute seminar – 16 September – Cesare Furlanello, Ph.D. (Italy)
The challenge of reproducibility of AI algorithms: from omics to digital pathology Monday 16 September 2019 – 12:00-13:00 Cesare Furlanello, Ph.D. (MPBA: Predictive Models for Biomedicine and Environment, FBK – Fondazione Bruno Kessler, Italy) Host : Gisèle Bonne Institute of Myology auditorium Hôpital de la Pitié-Salpêtrière Building Babinski Entrance 82 bd Vincent Auriol metro … [Read more]
COX6A2 variants cause a muscle-specific cytochrome c oxidase deficiency
Cytochrome c oxidase (COX) deficiency is a major mitochondrial respiratory chain defect that has vast genetic and phenotypic heterogeneity. This study aims to identify novel causative genes of COX deficiency with only striated muscle-specific symptoms. Whole exome sequencing was performed in 2 unrelated individuals who were diagnosed with congenital myopathy and presented COX deficiency in … [Read more]
