Blog Archives
Targeted inhibition of ORAI1 reduces tubular aggregates in mice
Tubular aggregate myopathy may be due to overactivation of Store Operated Ca2+ Entry (SOCE) as a result of a gain-of-function variant in the STIM1 or ORAI1 genes. ORAI1 is a T-tubule membrane calcium channel that is activated by STIM1, a sarcoplasmic reticulum membrane protein that senses depletion of intracellular calcium stores. KO mice for ORAI1 … [Read more]
Changes in screening criteria for late-onset Pompe disease in China
An initial screening campaign for late-onset Pompe disease (LOPD) in China in 2022 showed, as a warning sign, a predominance of respiratory involvement and less frequent hyperCKaemia. A new campaign was carried out on 726 patients, with an average age of 37.6, including 96 children under 14: 51.1% presented with hyperCKaemia, 57.9% with limb-girdle muscular … [Read more]
A promising ex vivo gene therapy for Pompe disease
International researchers have developed a lentivirus-based gene therapy which they have tested in a mouse model of Pompe disease: the lentiviral vector is used to incorporate the drug gene into the host genome, in this case the mouse model of Pompe disease, The target tissue was haematopoietic stem cells, the efficacy in producing the enzyme … [Read more]
Mavacamten for 4 weeks does not improve the condition of mice models of nebulin-related nemalin myopathy
In muscle fibers from individuals with nebulin-related nemaline myopathy (NEB-NM) and in NEB-NM mouse models, the proportion of myosin in the disordered relaxed state and ATP consumption are abnormally increased, accompanied by a reshuffling of the energy proteome of these cells. Mavacamten, which reduces the amount of myosin in the disordered relaxed state in hypertrophic … [Read more]
Loss of function of JPH1, which encodes junctophilin, causes congenital myopathy
Four individuals from unrelated consanguineous families, two of European origin, one of Khmer origin and one of Middle Eastern origin all presented with congenital myopathy with: neonatal hypotonia, difficulty sucking, cleft palate, club feet ; generalized weakness predominantly in the lower limbs; myopathic facies, bilateral ptosis, ophthalmoplegia and fatigability; muscle biopsy revealed a predominance of … [Read more]
Riboflavin transporter deficiency: the importance of treating early, even if it doesn’t solve everything
A retrospective study describes a population of 11 children with riboflavin transporter deficiency (RTD) type 2, all carriers of mutations in the SLC52A2 gene, followed up between 2012 and 2022: the most frequent first symptom was ataxia (n=9), followed by hearing loss (n=4), nystagmus (n=2) and upper limb weakness (n=1); the mean age of onset … [Read more]
Cerebral abnormalities in dysferlinopathies?
Slovakian and Austrian clinicians report the case of a family in which dysferlin deficiency was identified at the same time as structural and functional cerebral anomalies: the non-consanguineous family included four individuals (two sisters and two brothers) with a predominantly distal muscle phenotype (Miyoshi type), two pathological variants of the DYSF gene were identified (c.4076T>C … [Read more]
Towards a new therapeutic approach to cardiovascular complications in progeria?
Hutchinson-Gilford syndrome (HGPS or progeria) is an autosomal dominant disease caused by a mutation in the LMNA gene, coding for type A lamins, which results in a truncated form of pre-lamin A called progerin. Although asymptomatic at birth, patients develop symptoms such as accelerated ageing, growth retardation and loss of vascular smooth muscle cells (VSMC) … [Read more]
Thrombotic microangiopathy: a formidable complication of gene therapy
A multidisciplinary group of international experts has examined one of the complications that can arise during systemic gene therapy protocols, particularly in children with spinal muscular atrophy (SMA): thrombotic microangiopathy (TMA) is an immune runaway phenomenon linked to complement activation, with potentially dramatic consequences, Based on published data and their real-life experience with SMA, the … [Read more]
A multi-factorial approach to urinary disorders in DMD
Turkish physiotherapists report on their experience in assessing symptoms, disorders and signs of the lower urinary tract in children with Duchenne muscular dystrophy (DMD): 45 children and adolescents aged 5-18 years with DMD were included in the study, Assessments included a functional score assessing bladder emptying and the risk of urinary incontinence, a Vignos score, … [Read more]
