Lysosomal Storage Disorders Research

Early atrial remodelling drives arrhythmia in Fabry Disease

This study identifies early atrial remodelling as a driver of arrhythmia in Fabry Disease by combining ECG analysis, iPSC-derived cardiomyocytes, and in-silico modelling.

Bidirectional regulation of glycoprotein nonmetastatic melanoma protein B by β-glucocerebrosidase deficiency in GBA1 isogenic dopaminergic neurons from a patient with Gaucher disease and parkinsonism

The paper investigates how GBA1 mutations affect glycoprotein nonmetastatic melanoma protein B (GPNMB) expression in dopaminergic neurons, linking lipid accumulation to Parkinson's disease risk.

RNF13 is a novel interactor of iduronate 2-sulfatase that modifies its glycosylation and maturation

This study identifies RNF13 as an interactor of IDS that modifies its glycosylation and maturation, revealing its role in lysosomal trafficking and degradation.

Secondary deficiency of neuraminidase 1 contributes to CNS pathology in neurological mucopolysaccharidoses via hypersialylation of brain glycoproteins

This study shows that reduced NEU1 activity in neurological MPS leads to hypersialylation of brain glycoproteins, contributing to CNS pathology through disrupted synaptogenesis and behavior.

AAV gene therapy for GBA-PD and Gaucher Disease

This paper describes an AAV-mediated gene therapy strategy for GBA1-PD and Gaucher Disease, demonstrating robust GCase replenishment and cross-correction in preclinical models.

Neonatal systemic gene therapy restores cardiorespiratory function in a rat model of Pompe disease

Dissecting the biological impact of GBA1 mutations using multi-omics in an isogenic setting

The paper investigates the biological impact of GBA1 mutations using multi-omics in isogenic iPSC lines, finding limited overlapping results across cell types and suggesting RNA-based quantitation may not be optimal for characterizing GCase mechanisms.

Genomic Modifiers of Neurological Resilience in a Niemann-Pick C family

The paper identifies genomic modifiers of neurological resilience in Niemann-Pick C disease by analyzing exomes from a family with diverse phenotypes and validates findings in yeast models.

Expression study of Krabbe Disease GALC missense variants -- Insights from quantification profiles of residual enzyme activity, secretion and psychosine levels

This study quantifies the functional impact of GALC missense variants in Krabbe disease, showing strong correlations between residual enzyme activity, clinical severity, and psychosine levels.

Pharmacological GCase Activity Enhancement Inhibits Tau Accumulation

The paper shows that increasing GCase activity reduces Tau accumulation in fibroblasts with GBA1 mutations, suggesting it could be a therapeutic strategy for neurodegenerative diseases.

CLN5 deficiency impairs glucose uptake in Batten disease

This study develops a zebrafish model of CLN5 deficiency, revealing impaired glucose metabolism as a novel feature of NCL.

Is Gauchian genotyping of GBA1 variants reliable?

The paper evaluates the reliability of Gauchian for detecting GBA1 variants in whole genome sequencing, finding it misses some rare mutations and misreports genotypes due to database limitations.

PLA2G15 is a Lysosomal BMP Hydrolase and Its Targeting Ameliorates Lysosomal Disease

This study identifies PLA2G15 as a lysosomal BMP hydrolase and shows its targeting improves lysosomal disease symptoms in NPC1 models.

A novel class of allosteric glucosylceramidase beta 1 correctors that reduce cellular stress and enhance lysosomal function

This paper develops two allosteric GCase correctors that improve folding and lysosomal function in GD patient fibroblasts, reducing cellular stress and offering potential therapy for GD, PD, and Dementia with Lewy Bodies.

Genome-wide association study of glucocerebrosidase activity modifiers.

This study identifies genetic variants associated with glucocerebrosidase activity using GWAS in two cohorts, finding GBA1 variants and a novel association in the GAA locus.

N-Acetyl-l-Leucine (NALL) rescues inter-organelle communication in Niemann-Pick disease type-C patient cells.

The paper shows NALL rescues inter-organelle communication and restores lysosomal and mitochondrial function in NPC patient cells.

Targeted long-read RNA sequencing reveals the complexity of CLN3 transcription and the consequences of the most common 1-kb deletion in patients with juvenile CLN3 disease

The paper uses long-read RNA sequencing to analyze CLN3 transcription complexity and the impact of a common 1-kb deletion in juvenile CLN3 disease, revealing multiple transcripts and isoforms.

Tay-Sachs and Sandhoff Diseases: Diffusion tensor imaging and correlational fiber tractography findings differentiate late-onset GM2 Gangliosidosis

This study uses diffusion tensor imaging and correlational fiber tractography to show neurobiological differences between Tay-Sachs and Sandhoff diseases, with greater cerebellar pathology in Tay-Sachs patients.

Substrate reduction therapy in a Drosophila melanogaster model of Sanfilippo syndrome

This study tests a novel substrate reduction therapy using a GlcNAc analogue inhibitor in Sanfilippo syndrome models, showing reduced heparan sulfate accumulation in cells and Drosophila.

Subtle Cellular Phenotypes Inform Pathological and Benign Genetic Mutants in the Iduronidase-2 Sulfatase Gene

This study uses genome-engineered cells with IDS mutations to identify subtle lysosomal and membrane phenotypes that correlate with genetic variants in the IDS gene, improving the assessment of variant pathogenicity.

Reproducibility of PD patient-specific midbrain organoid data for in vitro disease modelling.

This study evaluates the reproducibility of midbrain organoid data from healthy individuals and GBA-N370S PD patients across batches and time points, showing consistent transcriptomic and metabolic signatures.

Rescue of lysosomal acid lipase deficiency in mice by rAAV8 liver gene transfer.

The paper develops a liver-targeted gene therapy using recombinant AAV8 to cure Lysosomal acid lipase deficiency by correcting lipid accumulation and normalizing gene expression and mitochondrial function in a mouse model.

Small-molecule Activation of TFEB Alleviates Niemann-Pick Disease Type C via Promoting Lysosomal Exocytosis and Biogenesis

This study shows that activating TFEB with sulforaphane reduces cholesterol accumulation in NPC1 models by enhancing lysosomal exocytosis and biogenesis.

Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease

This study shows that ASO-mediated Gys1 knockdown in a mouse model of Pompe disease reduces glycogen accumulation and improves motor function, both alone and in combination with ERT.

Novel cytometry-based characterization of lysosomal storage disease affected patient's cells

This paper characterizes lysosomal storage disease using imaging and cytometry to assess lipid homeostasis in patient cells and validates findings in alternative models.

Quantitative profiling of lysosomal accumulation through label-free biomarkers via High-Content Holo-Tomographic Flow Cytometry

This paper introduces HTFC to quantify lysosomal accumulation in LSDs, identifies novel biomarkers, and links 3D lysosomal structure to therapeutic efficacy.

Plasma glucosylceramide levels are regulated by ATP10D and are not involved in Parkinson's disease pathogenesis.

The paper investigates the role of ATP10D and GlcCer in Parkinson's disease, finding ATP10D regulates plasma GlcCer levels but is not involved in PD pathogenesis.

Inhibition of cathepsin B blocks amyloidogenesis in the mouse models of neurological lysosomal diseases mucopolysaccharidosis type IIIC and sialidosis

This study shows that inhibiting cathepsin B reduces amyloid deposits in mouse models of lysosomal diseases, suggesting it as a potential therapeutic target.

Niemann-Pick C-like endo-lysosomal dysfunction in DHDDS patient cells, a congenital disorder of glycosylation, can be treated with miglustat

This study shows that DHDDS patient cells exhibit lysosomal dysfunction and lipid accumulation, which can be mitigated by miglustat, a treatment approved for NPC disease.

Unravelling a mechanistic link between mitophagy defect, mitochondrial malfunction, and apoptotic neurodegeneration in MPS VII

This study identifies a causal link between mitophagy defects, mitochondrial dysfunction, and apoptotic neurodegeneration in MPS VII using a Drosophila model.