Lysosomal Storage Disorders Research

This study identifies inflammation and autophagy dysfunction, linked to mTOR pathway activation, as key mechanisms in metachromatic leukodystrophy using postmortem tissue analysis.

This study investigates the effects of Gba1 E326K mutation in mice, showing increased microglia activation, neuroinflammation, and dopaminergic neurodegeneration.

This study characterizes two novel human GCase antibodies for use in various assays to advance Parkinson disease research.

This study creates a neuronal in vitro model of Fabry disease to investigate small fibre neuropathy mechanisms, finding Gb3 accumulation, altered ion channel function, and mitochondrial trafficking issues.

This study shows that cardiac biopsies from Fabry disease patients exhibit significant cellular stress and irreversible damage before Gb3 inclusion bodies form, suggesting earlier treatment initiation is needed.

This study creates zebrafish models of MPS IIIA, IIIB, and IIIC, revealing hyperactivity, neuroinflammation, and oligodendrocyte changes similar to human disease.

This study shows that altered GM1 catabolism disrupts ER-PM junctions, increases Ca2+ signaling, and promotes synaptic spine formation in a neurodegenerative disease model.

This paper shows gene therapy prevents bowel motility issues and enteric neuron loss in mouse models of lysosomal storage diseases.

This study creates mouse models overexpressing mutant CSP/DNAJC5 and shows they develop neuronal lipofuscinosis and GRODs, while CSP/DNAJC5 deficiency does not.

This study shows that individual granulins can rescue disease pathology in PGRN-deficient mice, suggesting they are functional units of PGRN with therapeutic potential.

The paper uses long-read sequencing to accurately identify GBA variants as a major genetic risk factor for Parkinson's disease in a Luxembourg cohort.

The paper evaluates Oxford Nanopore sequencing for detecting GBA variants in Parkinson's disease patients and controls, finding high true-positive rates and identifying two pathogenic variants.

A single intravenous dose of AAV9-hGAA gene therapy improved motor milestones and GAA enzyme activity in an infant with infantile-onset Pompe disease.

This study corrects GBA mutations in hiPSCs to restore macrophage function in Gaucher disease and shows increased susceptibility to Mycobacterium tuberculosis.

The paper identifies small molecule compounds that reduce cholesterol accumulation in human NPC1 mutant fibroblasts but not in NPC1-/- cells, suggesting on-target effects.

This paper analyzes clinical data from NEDMABA cases to identify phenotype clusters and survival probabilities using MCA and Kaplan-Meier estimation.

The paper uses a zebrafish model of MPS IIIA to identify synaptic activity deficiencies as a key driver of disease progression through systems-level omics analyses and a novel bioinformatic tool.

This study shows that CD8+ T-cell depletion prevents myelin pathology in a mouse model of Globoid Cell Leukodystrophy.

This study identifies defective proteostasis of mutated AGAL causing ER stress and UPR in non-classic Fabry disease, independent of lysosomal storage.

The paper identifies genetic modifiers of alpha-synuclein-mediated neurodegeneration by screening fly homologs of lysosomal storage disorder genes.

This study genetically corrects iPSC-derived neural stem cells to deliver a modified NAGLU enzyme, reducing disease pathology in Sanfilippo B mice.

This paper generates and characterizes a Gaa c.1935C>A knock-in mouse model of infantile-onset Pompe disease, showing reduced GAA activity, glycogen accumulation, and cardiac hypertrophy.

This study shows that adenine base editors can correct 41% of GLB1 pathogenic SNVs in patient-derived fibroblasts, restoring β-gal activity without significant off-target effects.

This study identifies novel disease phenotypes in Cln2R207X mice, including cortical interneuron loss and seizure generation, providing insights into CLN2 disease pathogenesis.

This study identifies alpha-synuclein accumulation as a mediator of podocyte injury in Fabry disease, showing that targeting SNCA improves lysosomal function beyond enzyme replacement therapy.

This study shows that loss of PPT1, a depalmitoylating enzyme, leads to exaggerated synaptic upscaling and neuroinflammation in a lysosomal storage disease.

This paper demonstrates that oral administration of ground transgenic tobacco seeds expressing human GAA (tobrhGAA) improves symptoms and enzyme activity in Pompe disease knockout mice.

This study reports the formation of multinucleated globoid cells from Krabbe iPSC-derived microglia, which is absent in healthy or MLD donors, suggesting a potential functional impairment in disease progression.

This study shows that rhNAGLU-IGF2 treatment improves disease markers, behavior, and survival in Sanfilippo B mice and dogs.