Lysosomal Storage Disorders Research

Modelling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.

This paper develops a haploid cell model for Niemann-Pick disease type C to characterize patient variants and enable clinical interpretation.

Nanopore sequencing of the glucocerebrosidase (GBA) gene in a New Zealand Parkinsons disease cohort

The paper uses nanopore sequencing to identify GBA variants in a Parkinson's disease cohort, finding several risk variants and a higher dementia prevalence among carriers.

Insilico Analysis Reveal Three novel nsSNPs May effect on GM2A protein Leading to AB variant of GM2 gangliosidosis

The paper identifies four damaging SNPs in the GM2A gene, three of which are novel, and predicts their impact on protein structure and function, potentially contributing to AB variant of GM2 gangliosidosis.

Comprehensive Analysis of HEXB Protein Reveal Forty Two Novel nsSNPs That May Lead to Sandhoff disease (SD) Using Bioinformatics

This study identifies 42 novel non-synonymous SNPs in the HEXB gene potentially linked to Sandhoff disease using bioinformatics analysis.

A Drosophila model of neuronal ceroid lipofuscinosis CLN4 reveals a hypermorphic gain of function mechanism

This study develops a Drosophila model of CLN4 NCL, showing that CLN4 mutations cause hypermorphic gain of function through excessive oligomerization and impaired membrane trafficking.

Genetic modifiers of risk and age at onset in GBA associated Parkinson disease and Lewy body dementia

The paper identifies genetic modifiers of risk and age at onset in GBA-associated Parkinson disease and Lewy body dementia using large case-control datasets and genome-wide association studies.

Thirty two novel nsSNPs May effect on HEXA protein Leading to Tay-Sachs disease (TSD) Using a Computational Approach

The paper predicts 32 novel non-synonymous SNPs in the HEXA gene that may contribute to Tay-Sachs disease using bioinformatics tools.

Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I

This study uses CRISPR/Cas9 to edit hematopoietic stem cells to express iduronidase, correcting Mucopolysaccharidosis type I in mice.

Managing the Spatial Covariance of Genetic Diversity in Niemann-Pick C1 Through Modulation of the Hsp70 Chaperone System

The paper shows that modulating the Hsp70 chaperone system improves NPC1 protein trafficking and stability across diverse genotypes by altering spatial covariance tolerance.

Neonatal brain-directed gene therapy rescues a mouse model of neurodegenerative CLN6 Batten disease

This study shows that neonatal brain-directed gene therapy using AAV9-CLN6 significantly improves survival, motor function, and reduces neuropathology in a mouse model of CLN6 Batten disease.

Oncogenic effects of germline mutations in lysosomal storage disease genes

This study identifies germline mutations in lysosomal storage disease genes as risk factors for cancer, showing increased cancer risk and earlier onset in mutation carriers.

Unexpected opposing biological effect of genetic risk factors for Parkinson disease

The paper investigates the additive effect of genetic risk variants for Parkinson's disease and finds an unexpected rescue effect on neuronal function and survival in zebrafish with combined GCase and ASM deficiency.

Progranulin deficiency leads to reduced glucocerebrosidase activity

This study shows that progranulin deficiency reduces glucocerebrosidase activity, linking it to lysosomal dysfunction in neurodegenerative diseases.

The neuronal ceroid lipofuscinosis protein Cln7 regulates neural development from the post-synaptic cell

This study shows that Cln7 regulates synaptic growth and function in Drosophila, with implications for neuronal ceroid lipofuscinosis pathology.

BMN 250, a fusion of lysosomal alpha-N-acetylglucosaminidase with IGF2, exhibits different patterns of cellular uptake into critical cell types of Sanfilippo syndrome B disease pathogenesis.

This study characterizes two distinct cellular uptake mechanisms for BMN 250 in Sanfilippo B disease, showing CI-MPR-mediated uptake in neurons and astrocytes and receptor-independent uptake in microglia.

Detection of GBA missense mutations and other variants using the Oxford Nanopore MinION

The paper validates the use of Oxford Nanopore MinION for detecting GBA mutations, including missense variants and deletions, with accurate phasing and intronic analysis.

Utilizing ExAC to Assess the Hidden Contribution of Variants of Unknown Significance to Sanfilippo Type B Incidence

The paper estimates the contribution of variants of unknown significance to Sanfilippo Type B incidence using functional activity data and population allele frequencies.

Arimoclomol as a potential therapy for neuronopathic Gaucher Disease

This study shows arimoclomol improves GCase function in GD models by enhancing its folding, maturation, activity, and localization.

Tolerance of chronic HDACi-administration used for treatment of neurological and visceral disease including lung pathogenesis.

This study shows that chronic administration of a triple HDACi formulation is well-tolerated in mice, preserving brain and lung function while improving drug delivery to the brain and lungs.

The mechanism of sphingolipid processing revealed by a GALC-SapA complex structure

The paper reveals the structure of the GALC-SapA complex, showing how it processes glycosphingolipids and explains saposin binding specificity.

A Saposin deficiency model in Drosophila: lysosomal storage, progressive neurodegeneration, sensory physiological decline and defective calcium homeostasis

This paper characterizes a Drosophila model of saposin deficiency, showing lysosomal storage, neurodegeneration, and calcium homeostasis defects similar to human LSDs.