Lysosomal Storage Disorders Research

This study shows that HDAC6 inhibition with ACY-738 improves early neuropathology and neuronal defects in a mouse model of Krabbe 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 study tracks the clinical progression of NGLY1 Deficiency in 29 patients over 32 months, identifying key symptoms and biomarkers for future trial endpoints.

This paper presents a novel porcine model of CLN3 Batten disease that recapitulates clinical phenotypes observed in humans.

This study identifies biomarkers predicting avascular osteonecrosis risk in Gaucher disease patients on enzyme replacement or substrate reduction therapy.

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

The paper examines the relationship between glucocerebrosidase activity, lipid levels, and protein pathologies in Parkinson's disease and dementia with Lewy bodies.

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.

This study shows that CLN3 deficiency disrupts stress granule dynamics and translation, linking it to neurodegenerative disease mechanisms.

This paper describes a zebrafish model of NPC1 deficiency with a C-terminal mutation, showing severe phenotypes and altered lipid metabolism.

This study demonstrates that gene therapy using hematopoietic stem cells can mitigate CLN1 disease symptoms in mice, with enhanced benefits from hPPT1 overexpression and combined transplantation approaches.

The paper examines how a polygenic Parkinson's disease genetic risk score modifies the risk of parkinsonism in Gaucher disease patients.

This study uses a novel proteomics platform to identify PTM dysregulation in GBA-N370S PD neurons, revealing impaired neuritogenesis and a role for tau.

This study corrects a mutation in a mouse model of Hurler syndrome using in vivo adenine base editing, showing reduced GAG accumulation and neurobehavioral deficits.

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.

The paper identifies ceramide accumulation, lysosomal expansion, and mitochondrial defects as root causes of INAD/PARK14 and tests therapeutic strategies including drugs and gene therapy.

The paper creates a database and browser for GBA1 variants associated with Parkinson's Disease, classifying them into severe, mild, and risk categories.

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 shows that the GBA1 L444P mutation increases glucosylsphingosine levels and hippocampal alpha-synuclein inclusions in mice, contributing to synucleinopathy pathology.

This study examines CLN3 disease using patient-derived cortical neurons, finding reduced electrophysiological activity and lysosomal alterations.

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 paper presents baseline data from a registry of eight gangliosidoses, quantifying disease severity and highlighting diagnostic delays and phenotypic characteristics.

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 a missense mutation in VPS33A causing an attenuated juvenile form of mucopolysaccharidosis plus and shows potential therapeutic interventions.