Lysosomal Storage Disorders Research

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

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.

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.

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

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.

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.

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.

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

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

This study shows that GBA1 variants increase Parkinson's disease risk, with severe variants having higher risk than risk variants, and polygenic scores further increase this risk.

This study investigates how GCase deficiency in human astrocytes affects lipid metabolism and its impact on dopaminergic neurons in a PD model, finding impaired lipid metabolism and increased inflammation.

This paper evaluates the combination of Miglustat and Ambroxol in a virtual trial for Type 1 Tay-Sachs Disease using aiHumanoid simulations, showing improved outcomes at intermediate doses.

This study identifies acid ceramidase as a potential therapeutic target for Niemann-Pick C disease by reducing lipid accumulation in a cellular model.

This study investigates how lysosomal dysfunction in microglia drives epigenetic and transcriptional changes in a mouse model of Sanfilippo syndrome, revealing shared mechanisms with Alzheimer's disease.

This study shows that myeloid-derived β-hexosaminidase supports neuronal lysosomal function and that microglial replacement can reverse Sandhoff disease symptoms.

The paper investigates a pseudodeficiency allele in Pompe disease, clarifies its benign classification, and highlights the importance of accurate variant interpretation in genetic diagnosis.

This study develops i3Neuron models of Tay-Sachs and Sandhoff diseases, revealing plasma membrane remodeling and synaptic dysfunction due to GM2 ganglioside accumulation.

This study examines alpha-synuclein pathology in metachromatic leukodystrophy (MLD) brain tissue, finding seed-competent alpha-synuclein conformers in juvenile-onset cases, similar to Lewy body diseases.

This study shows that GBA1 mutations in dopamine neurons reduce VGLUT2 expression, increase firing rate, and cause structural changes linked to Parkinson's disease.

The paper identifies plasma proteomic signatures associated with MLIV, showing decreased neuronal proteins and increased muscle proteins, with specific markers correlating with disease severity.

This paper shows that delivering GBA1 via AAV reduces alpha-synuclein aggregates and restores motor function in disease models.

The paper characterizes sleep disturbances in a mouse model of CLN3 disease, finding sex-specific differences in sleep patterns compared to wild-type controls.

The paper identifies transcription factors that regulate β-glucocerebrosidase activity, showing that USF2 and ONECUT2 have opposing effects on GCase levels and function.

This study identifies Smpd1's role in tracheal gas-filling in Drosophila embryos by regulating ceramide-specific chitin-clearance, showing that lipid metabolism defects contribute to respiratory dysfunction.

AAV-BR1-NPC2 gene therapy reduces cholesterol deposition and neurological symptoms in NP-C2 mice by delivering NPC2 to brain endothelial cells and neurons.

This study identifies PPT1's role in regulating GABAAR palmitoylation, showing its impact on synaptic transmission and circuitry oscillation in CLN1 disease.

The paper develops CLN6 patient-derived iPSC models to study neurodegeneration, finding significant lysosomal and synaptic pathway changes in differentiated neurons.

This paper investigates the use of ground germinated barley (GGB) as an oral enzyme replacement therapy (Oral-ERT) for Pompe disease in knockout mice, showing it can reverse enzyme defects and improve clinical phenotypes.

The paper uses long-read RNA sequencing to analyze CLN3 transcript complexity in healthy samples, identifying over 100 novel transcripts and 48 ORFs, with the canonical isoform being the most abundant.

This study shows that sortilin inhibition with AF38469 improves lysosomal and glial pathology in multiple Batten disease models.