Lysosomal Storage Disorders Research

This study shows that a Gnptab variant impairs fine motor skills in mice by affecting grasp shaping and trajectory control.

The paper characterizes early CLN7 disease in macaques using multimodal biomarkers, revealing region-specific brain changes and neurodegeneration markers.

This study shows that modGLA mRNA therapy reverses Fabry disease phenotypes in human iPSC-derived cardiomyocytes by restoring enzyme activity and normalizing molecular alterations.

This paper generates a Cln8 p.R24G mouse model that phenocopies major clinical features of Northern epilepsy, including seizures and neurodegeneration.

This study models Fabry disease in human sensory neurons and finds axon guidance deficits and reduced neurite length due to Gb3 accumulation, with partial rescue by AGAL enzyme supplementation.

This study shows that chronic cannabidiol treatment delays or prevents seizures in a mouse model of CLN2 disease without affecting traditional neuroimmune markers.

This study compares cognitive decline and white matter changes in Fabry disease patients to typical aging, finding microstructural damage in younger patients and progressive tissue damage with age.

The paper assesses the contribution of unknown GBA1 variants to Parkinson's disease risk and their relevance for clinical trial stratification.

This study shows that trehalose activates Mitf, improving autophagy and reducing neurodegeneration in a Drosophila model of MPS VII.

The paper expands the clinical, biochemical, and brain imaging phenotype spectrum of β-mannosidosis by analyzing 44 patients and describing new features and genetic variants.

This study investigates sex-specific and age-related auditory neurophysiological deficits in Cln3-/- mice using MMN paradigms, revealing central auditory processing issues that mirror human CLN3 disease findings.

This paper develops patient-specific midbrain organoids with CRISPR correction to model neuronopathic Gaucher disease and test therapies.

This study shows that loss of CLN3 disrupts lysosomal lipid metabolism, leading to nuclear envelope lipid changes, DNA damage, and YAP1-driven apoptosis in Batten disease models.

This study identifies muscle energy crisis as the initial driver of locomotor dysfunction in β-glucuronidase-deficient Drosophila, showing muscle-specific ATP depletion and autophagy defects precede neurological symptoms.

A splice-switching antisense oligonucleotide delivered via intravitreal injection mitigates early retinal dysfunction in a pig model of CLN3 Batten disease.

The paper identifies a splice variant-dependent localization of PMCA2 to lysosomes and links it to neurodegenerative diseases.

This study investigates the relationship between mitochondrial stress markers and clinical outcomes in Fabry disease patients, finding that Hsp60 levels correlate with disease severity in specific genotypes.

The paper uses multi-omics analysis of lysosomes to identify age-related sphingolipid catabolism changes linked to lysosomal dysfunction in the aging brain.

This study identifies small molecules that restore Golgi morphology and neurite outgrowth in Cohen Syndrome models by modulating sphingolipid metabolism.

This study shows the PD-risk GBA1 variant E326K reduces lysosomal GCase activity by disrupting LIMP2 interaction and causes lysosomal and mitochondrial dysfunction.

The paper shows that reducing heparan sulfate in cerebrospinal fluid reflects brain neuron correction in Sanfilippo B mice through targeted enzyme delivery.

This study identifies pregnenolone as a therapeutic candidate for CLN2 disease by suppressing seizures and normalizing lysosomal function in tpp1-/- zebrafish.

The paper identifies CHIP-mediated microautophagy as a protective mechanism against lysosomal damage caused by CLN4 mutations, showing its therapeutic potential in neurodegenerative diseases.

This study investigates the role of GABAergic interneurons in seizure progression and mortality in CLN2 disease mice, finding that interneuron dysfunction contributes to epileptic seizures and death.

This study compares systemic neonatal and intracerebroventricular AAV9 gene therapy in Npc1-deficient mice, finding that systemic neonatal delivery achieves comparable survival and phenotypic improvements to ICV delivery.

The paper identifies Neurexin-2 downregulation in a mouse model of PMM2-CDG and shows it can be reversed by AAV9-PMM2 gene treatment.

This study shows that redox imbalance in Drosophila models of Gaucher and Parkinson's disease leads to renal dysfunction, which contributes to systemic decline and neurodegeneration.

This study investigates the role of glycosphingolipids in autoimmune manifestations and myeloma in Gaucher disease using a mouse model and finds that CD1 molecules regulate inflammation and tumour formation but not monoclonal immunoglobulin production.

This study uses a 3D iPSC retina model to show that acid ceramidase deficiency causes sphingolipid metabolism changes and photoreceptor degeneration in CLN3 disease, with therapeutic potential for rhAC.

The paper compares dopaminergic neurons from siblings with Gaucher disease to investigate genetic factors contributing to Parkinsonism.