Lysosomal Storage Disorders Research

Neuronal lipofuscinosis caused by Kufs disease/CLN4 DNAJC5 mutations but not by a CSPα/DNAJC5 deficiency

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

Granulins rescue inflammation, lysosome dysfunction, and neuropathology in a mouse model of progranulin deficiency.

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

Accurate long-read sequencing identified GBA variants as a major genetic risk factor in the Luxembourg Parkinson's study

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 Batten disease protein CLN3 is important for stress granules dynamics and translational activity.

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

Severe neurometabolic phenotype in npc1-/- zebrafish with a C-terminal mutation

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

An innovative hematopoietic stem cell gene therapy approach benefits CLN1 disease in the mouse model

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.

Polygenic Parkinson's disease genetic risk score as risk modifier of parkinsonism in Gaucher disease

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

A novel post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson's disease GBA-N370S dopamine neurons

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

In vivo adenine base editing corrects newborn murine model of Hurler syndrome

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.

GBA in Parkinson's disease: variant detection and pathogenicity scoring matters

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.

Exploring therapeutic strategies for Infantile Neuronal Axonal Dystrophy (INAD/PARK14)

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.

Classification of GBA1 variants in Parkinson disease; the GBA1-PD browser

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

First-in-human case report: AAV9-hGAA gene therapy for a patient with infantile-onset Pompe disease.

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

Neuronopathic GBA1 L444P mutation accelerates glucosylsphingosine levels and formation of hippocampal alpha-synuclein inclusions

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

Lysosomal alterations and decreased electrophysiological activity in CLN3 disease (966 bp deletion, E295K) patient-derived cortical neurons

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

CRISPR correction of GBA mutation in hiPSCs restores normal function to Gaucher macrophages and increases their susceptibility to Mycobacterium tuberculosis

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

Screening of small molecule chemical library identifies leads that reduce cholesterol accumulation in human NPC1 fibroblasts

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

Meta-Analysis of Clinical Phenotype and Patient Survival in Neurodevelopmental Disorder with Microcephaly, Arthrogryposis, and Structural Brain Anomalies Due to Bi-allelic Loss of Function Variants in SMPD4

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

Systems-level investigation of mucopolysaccharidosis IIIA identifies deficient synaptic activity as a key driver of disease progression

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.

Quantitative longitudinal natural history of eight gangliosidoses - conceptual framework and baseline data of the German 8-in-1 disease registry. A cross-sectional analysis.

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

Therapeutic depletion of CD8+ T-cells prevents myelin pathology in Globoid Cell Leukodystrophy

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

AGAL misprocessing-induced ER stress and the unfolded protein response: lysosomal storage-independent mechanism of Fabry disease pathogenesis?

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

Juvenile Mucopolysaccharidosis plus disease caused by a missense mutation in VPS33A

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

The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines.

This study shows that the GBA E326K variant increases alpha-synuclein aggregation and lipid droplet accumulation in human cells without reducing GCase activity.

Transcriptome deregulation of peripheral monocytes in GBA-related Parkinson's disease

The paper identifies transcriptomic changes in monocytes from GBA mutation carriers with Parkinson's disease, highlighting dysregulated pathways related to alpha-synuclein degradation and lysosomal function.

Functional screening of lysosomal storage disorder genes identifies modifiers of alpha-synuclein mediated neurodegeneration

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

Comprehensive analysis of GBA using a novel algorithm for Illumina whole-genome sequence data or targeted Nanopore sequencing

The paper presents two methods to accurately detect GBA variants and reciprocal recombinants, showing higher GBA variant frequency in Lewy body dementia compared to Parkinson's disease.

Genetically corrected iPSC-derived Neural Stem Cell Grafts deliver NAGLU-IGFII fusion protein to affect CNS disease in Sanfilippo B Mice

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

CRISPR-Mediated Generation and Characterization of a Gaa Homozygous c.1935C>A (p.D645E) Pompe Disease Knock-in Mouse Model Recapitulates Human Infantile Onset-Pompe Disease

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.

Transmembrane Batten disease proteins interact with a shared network of vesicle sorting proteins to regulate synaptic composition and function.

This study identifies a shared protein network involving Batten disease proteins that regulates synaptic composition and function through interactions with vesicle sorting proteins.