Blog Archives
Safety and ventilatory outcomes in a phase I/II trial of AAV-mediated GAA gene therapy in Pompe disease
Pompe Disease is an inherited neuromuscular disease due to deficiency of lysosomal acid alpha-glucosidase (GAA) leading to glycogen accumulation in muscle and motoneurons. Cardiopulmonary failure in infancy leads to early mortality and GAA enzyme replacement therapy (ERT) results in improved survival, reduction of cardiac hypertrophy and developmental gains. However, many children have progressive ventilatory insufficiency … [Read more]
“State-of-the-heart” of cardiac laminopathies
The LMNA gene encodes the nuclear A-type lamins. LMNA mutations are associated with more than 10 clinical entities and represent one of the first causes of inherited dilated cardiomyopathy. LMNA-dilated cardiomyopathy is associated with conduction disease (DCM-CD) and is a severe and aggressive form of DCM. However, pathogenesis remains largely unknown and no specific treatment … [Read more]
Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease
A recently proposed therapeutic approach for lysosomal storage disorders (LSDs) relies upon the ability of transcription factor EB (TFEB) to stimulate autophagy and induce lysosomal exocytosis leading to cellular clearance. This approach is particularly attractive in glycogen storage disease type II [a severe metabolic myopathy, Pompe disease (PD)] as the currently available therapy, replacement of … [Read more]
Identification of the genetic cause of HMSN-P
Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P) has been reported as a rare type of autosomal dominant adult-onset Charcot-Marie-Tooth disease. HMSN-P has been described only in Japanese descendants since 1997, and the causative gene has not been found. In this genetic and observational analysis study, the authors aimed to identify the genetic cause … [Read more]
A mutation in the transportin 3 gene results in LGMD 1F
In 2001, the authors of the present study reported linkage of an autosomal dominant form of limb-girdle muscular dystrophy, limb-girdle muscular dystrophy 1F, to chromosome 7q32.1-32.2, but the identity of the mutant gene was elusive. Here, using a whole genome sequencing strategy, they identified the causative mutation of limb-girdle muscular dystrophy 1F, a heterozygous single … [Read more]
Mutations in GFPT1 that underlie limb-girdle congenital myasthenic syndrome result in reduced cell-surface expression of muscle AChR
Mutations in GFPT1 underlie a congenital myasthenic syndrome characterised by a limb-girdle pattern of muscle weakness. Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is a key rate-limiting enzyme in the hexosamine biosynthetic pathway providing building blocks for the glycosylation of proteins and lipids. It is expressed ubiquitously and it is not readily apparent why mutations in this gene … [Read more]
PPMD white paper lists several recommendations to speed up orphan drug approval
Parent Project Muscular Dystrophy (PPMD) is a patient advocacy foundation focused on advancing research that will lead to treatments for Duchenne and Becker muscular dystrophy (DMD and BMD). PPMD has released Putting Patients First, a white paper outlining recommendations to speed responsible access to new treatments for DMD and other, rare, serious, and life-threatening neurological … [Read more]
Non-surgical prevention and management of scoliosis for children with Duchenne muscular dystrophy: What is the evidence?
This review was performed to examine the evidence for non-surgical interventions for preventing scoliosis and the need for scoliosis surgery in children with Duchenne muscular dystrophy. Medline and Embase databases and reference lists from key articles were searched. After the inclusion and exclusion criteria were applied, 13 studies were critically appraised independently by two reviewers. … [Read more]
Development of a biomarker panel (SMA-MAP) for plasma proteins in SMA patients
Spinal Muscular Atrophy (SMA) presents challenges in (i) monitoring disease activity and predicting progression, (ii) designing trials that allow rapid assessment of candidate therapies, and (iii) understanding molecular causes and consequences of the disease. Validated biomarkers of SMA motor and non-motor function would offer utility in addressing these challenges. The objectives of this study were … [Read more]
SERCA2a gene therapy improves symptomatic heart failure in delta-sarcoglycan deficient animals
The loss of dystrophin or its associated proteins results in the development of muscle wasting frequently associated with a cardiomyopathy. Contractile cardiac tissue is injured and replaced by fibrous tissue or fatty infiltrates, leading to progressive decrease of the contractile force and finally to end-stage heart failure. At the time symptoms appear, restoration of a … [Read more]
