IntroductionMRI is an important noninvasive tool that can be used for monitoring progression of Duchenne muscular dystrophy (DMD). We present muscle volume (MV) and fat fraction (FF) measures from MRI examinations of ambulatory participants with DMD during 2 years of follow-up with fordadistrogene movaparvovec, a recombinant adeno-associated virus serotype-9-based gene therapy in development for DMD.MethodsIn this ongoing, phase 1b, open-label, nonrandomized study (NCT03362502), MRI assessments and functional data were evaluated following treatment with fordadistrogene movaparvovec. Eligible participants (N = 19; male, aged 4-12 years at enrollment), received a single intravenous infusion of low-dose (1E14 vg/kg) or high-dose (3E14 vg/kg) fordadistrogene movaparvovec. An external reference (ER) cohort from another interventional trial was derived from participants who met eligibility criteria for this trial.ResultsFordadistrogene movaparvovec-treated participants had a mean percent change from baseline (%CFB) in MV of 9.0 +/- 13.5% (1 year) and 7.4 +/- 16.1% (2 years). ER cohort had a respective mean %CFB in MV of 2.7 +/- 8.3% and 2.4 +/- 12.1%. MV increases were most pronounced in younger participants.ConclusionsMRI of thigh muscle and upper limb of participants treated with fordadistrogene movaparvovec showed increases in MV over 2 years. No clear difference in FF was seen in comparison to ER over 2 years.
There is a paucity of data demonstrating the safety and efficacy of intravenous tenecteplase in patients with acute ischemic stroke in the posterior circulation. Basilar artery occlusion (BAO), resulting from an interruption of blood supply to the vertebrobasilar system of cerebral arteries, is a major cause of severe posterior circulation strokes. A 65-year-old male patient was admitted to the Department of Neurology, Saarland University Medical Center with symptoms of acute ischemic stroke in the posterior circulation. Computed tomography (CT) angiography revealed an acute BAO. The patient was administered intravenous tenecteplase at a dose of 0.25 mg/kg. Following the patient's transfer to the catheterization room for the scheduled endovascular treatment, a notable improvement in symptoms was observed, with an initial National Institutes of Health Stroke Scale (NIHSS) score of 20 decreasing to 2. This substantial improvement precluded the necessity for any catheter intervention. Subsequent control CT angiography demonstrated recanalisation of the BAO after administration of intravenous tenecteplase. No hemorrhagic complications occurred. This case demonstrates that the administration of intravenous tenecteplase at a dose of 0.25 mg/kg in patients with BAO can result in successful reperfusion without symptomatic intracranial hemorrhage.
Background: Stroke remains a leading cause of death and disability worldwide, with ischemic stroke accounting for approximately 87% of cases. Although timely reperfusion is crucial for salvaging the ischemic penumbra, it can paradoxically exacerbate tissue damage through ischemia-reperfusion (I/R) injury. Recent studies have demonstrated that I/R significantly upregulates fatty acid binding protein 3(FABP3) expression, which has been shown to play a crucial role in mitochondrial dysfunction and neuronal apoptosis. However, the role of FABP3 in cerebral I/R injury remains poorly understood. Methods: Adult male C57BL/6 mice underwent transient middle cerebral artery occlusion (tMCAO) for 2 h followed by 24 h of reperfusion. Mice were randomly assigned to four groups (n = 5 per group): control (sham), model (I/R), negative control (sh-NC I/R), and experimental group (sh-FABP3 I/R). FABP3-specific shRNA lentivirus was administered via intracerebroventricular injection. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological function by behavioral scoring, and neuronal damage by hematoxylin-eosin (H&E) staining. Western blot analysis was performed to evaluate the expression of apoptosis-related proteins. Results: FABP3 expression was significantly upregulated following cerebral I/R injury. FABP3 knockdown markedly reduced infarct volume (20 +/- 3.16% vs. 35 +/- 2.43% in I/R group, p < 0.001) and improved neurological scores. Histological analysis revealed that FABP3 inhibition significantly attenuated neuronal damage in the penumbra cortex and hippocampal Cornu Ammonis area 1(CA1) region. Moreover, FABP3 knockdown decreased the expression of pro-apoptotic proteins (Bax, cleaved-caspase-3) while increasing anti-apoptotic Bcl-2 levels. Conclusions: This study demonstrates for the first time that FABP3 knockdown confers neuroprotection against cerebral I/R injury by suppressing neuronal apoptosis. These findings suggest that FABP3 is a promising therapeutic target for ischemic stroke treatment.
ObjectiveThe causal relationship between primary sclerosing cholangitis (PSC) and stroke risk remains unclear. We attempt to explore the causal relationship between PSC and stroke risk.MethodsA two-sample Mendelian randomization (MR) study was performed based on the genome-wide association study (GWAS) data to analyze the causal effect of PSC on the risk of stroke. The inverse-variance weighted (IVW), MR-Egger regression and weighted median were used for analysis.ResultsEighteen single-nucleotide polymorphisms (SNPs) associated with PSC were selected from GWASs as instrumental variables (IVs). The results of IVW methods showed that PSC was associated with a higher risk of stroke (beta = 0.0006, standard error [SE] = 0.0002, P = 0.017). Similarly, the results of MR-Egger methods showed consistent results (beta = 0.0008, SE = 0.0004, P = 0.045). Likewise, the association between PSC and stroke has been confirmed, using the weighted median methods (beta = 0.0009, SE = 0.0003, P = 0.006). The consistent results revealed a causal relationship between PSC and increased stroke risk. Cochran's Q test was used and low heterogeneity was identified (IVW. Q = 18.4, P = 0.364; MR-Egger. Q = 17.65, P = 0.345).ConclusionThe study results revealed that PSC might be causally associated with an increased risk of stroke.
