Biofabrication of anbone model for Gaucher disease.

Gaucher disease (GD), the most prevalent lysosomal disorder, is caused bygene mutations, leading to deficiency of glucocerebrosidase, and accumulation of glycosphingolipids in cells of the mononuclear phagocyte system. While skeletal diseases are the leading cause of morbidity and reduced quality of life in GD, the pathophysiology of bone involvement is not yet fully understood, partly due to lack of relevant human model systems. In this work, we present the first 3D human model of GD using aspiration-assisted freeform bioprinting, which enables a platform tool with a potential for decoding the cellular basis of the developmental bone abnormalities in GD.

Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants.

Population studies point to regional and ethnicity-specific differences in genetic predisposition for some lysosomal storage disorders (LSDs). The aim of the study was to determine the prevalence of the three treatable forms of lysosomal storage disorders (Gaucher disease [GD], Pompe disease [PD], and Fabry disease [FD]) in a cohort of mostly urban-dwelling individuals of African ancestry, a previously unknown genetic landscape for LSDs. Large-scale selective multistep biochemical and genetic screening was performed in patients seeking healthcare for various health concerns.

The Interaction of Innate and Adaptive Immunity and Stabilization of Mast Cell Activation in Management of Infusion Related Reactions in Patients with Fabry Disease.

Fabry disease (FD) is an X-linked lysosomal disorder caused by mutations in gene resulting in lack of or faulty α-galactosidase A (α-GalA) enzyme. Enzyme replacement therapy (ERT) with recombinant human α-GalA enzyme (agalsidase) is the standard treatment option for FD. Infusion-related reactions (IRRs), with symptoms ranging from rigors, to fever, pain, vomiting, angioedema and diarrhea, are often seen due to immune response against the exogenous enzyme.

Pregnancy Outcomes in Late Onset Pompe Disease.

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated.

Effect of Substrate Reduction Therapy in Comparison to Enzyme Replacement Therapy on Immune Aspects and Bone Involvement in Gaucher Disease.

Gaucher disease (GD) is caused by mutations in the gene, leading to deficient activity of the lysosomal enzyme glucocerebrosidase. Among all the symptoms across various organ systems, bone disease is a major concern as it causes high morbidity and reduces quality of life. Enzyme replacement therapy (ERT) is the most accepted treatment; however, there are still unmet needs.

Altered immune phenotypes in subjects with Fabry disease and responses to switching from agalsidase alfa to agalsidase beta.

Fabry disease (FD) is a rare X-linked genetic disorder caused by mutations in the gene encoding the lysosomal enzyme, α-galactosidase A (α-gal A). The mutations lead to lack of or faulty enzyme causing accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids including globotriaosylsphingosine (lyso-Gb). Treatment options for FD include enzyme replacement therapy.

Time of Initiating Enzyme Replacement Therapy Affects Immune Abnormalities and Disease Severity in Patients with Gaucher Disease.

Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study.

Gaucheromas: When macrophages promote tumor formation and dissemination.

Deficiency of the lysosomal enzyme, β-glucocerebrosidase, and accumulation of its substrate in cells of the reticuloendothelial system affects multiple organ systems in patients with Gaucher disease (GD). Lipid laden macrophages turn into Gaucher cells (GC) which are the pathological characteristic of GD. GC focally accumulate in the liver, spleen and at extraosseous sites to form benign lesions called Gaucheromas.

Enzyme replacement therapy reverses B lymphocyte and dendritic cell dysregulations in patients with Gaucher Disease.

Gaucher disease (GD) is caused by mutations in the GBA gene encoding lysosomal enzyme, β-glucocerebrosidase (GCase). GCase deficiency results in accumulation of its substrates in cells of macrophage lineage, affecting multiple organ systems. Enzyme replacement therapy (ERT) with recombinant human GCase is the standard of care to treat GD.

Persistent immune alterations and comorbidities in splenectomized patients with Gaucher disease.

Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the gene encoding acid-β-glucosidase, resulting in functional disruptions in degradation of glycosphingolipids and lysosomal accumulation of the substrates. The most frequent clinical presentations of GD are thrombocytopenia, splenomegaly and bone pain. Prior to advent of enzyme replacement therapy, splenectomy was performed for complications of hypersplenism such as severe thrombocytopenia and transfusion dependency.

A pilot study of omalizumab in eosinophilic esophagitis.

Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE), once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches.

Efficient procurement of epithelial stem cells from human tissue specimens using a Rho-associated protein kinase inhibitor Y-27632.

The efficient culture of stem cells from epithelial tissues such as skin and corneas is important for both experimental studies and clinical applications of tissue engineering. We now demonstrate that treatment of human-skin-derived keratinocytes with a Rho-associated protein kinase inhibitor Y-27632 for the initial 6 days of primary culture can increase the number of keratinocytes that possess stem cell properties to form colonies during in vitro culture of freshly isolated cells and subsequent passage (50-fold). Further, we show that Y-27632 treatment can increase the total number of prostate epithelial cells derived from human prostate specimens.