scholarly journals Development of Organelle Replacement Therapy Using a Stearyl-Polyhistidine Peptide against Lysosomal Storage Disease Cells

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2995 ◽  
Author(s):  
Hayashi ◽  
Okamoto ◽  
Kawano ◽  
Iwasaki
Keyword(s):  
Replacement Therapy ◽  
Lysosomal Storage Disease ◽  
Lysosomal Enzymes ◽  
Drug Delivery Systems ◽  
Metabolic Disorders ◽  
Storage Disease ◽  
Cell Penetrating Peptide ◽  
Lysosomal Storage ◽  
Hydrophobic Region ◽  
Normal Cells

We previously reported on a polyhistidine peptide, His16 peptide, as a new cell-penetrating peptide. This peptide is anticipated to be a new carrier for drug delivery systems (DDSs) for targeting intracellular lysosomes because it can transport macromolecules (e.g., liposomes) into these organelles. In the present study, we examined the application of His16 peptide as a DDS carrier against lysosomal storage disease (LSD) cells. LSDs are metabolic disorders caused by loss of specific lysosomal enzymes. For the treatment of LSD cells, we devised a system designated organelle replacement therapy (ORT). ORT is a strategy for transporting exogenous lysosomes containing all kinds of lysosomal enzymes from normal cells into endogenous lysosomes in LSD cells using His16 peptide. To develop the ORT system, we prepared His16 peptide-modified healthy lysosomes (His16-Lyso) by insertion of a stearyl-His16 peptide into a hydrophobic region in the lysosomal membrane. His16-Lyso showed cellular uptake and localization to endogenous lysosomes in LSD cells. His16-Lyso also restored the proliferation of LSD cells, which otherwise showed slower proliferation than normal cells. These results suggested that His16-Lyso replenished deficient lysosomal enzymes in LSD cells. The results further suggest that His16-Lyso are promising candidates as a treatment tool for LSD cells and to establish a foundation for ORT.

scholarly journals Intermittent enzyme replacement therapy with recombinant human β-galactosidase prevents neuraminidase 1 deficiency

2020 ◽  
Vol 295 (39) ◽  
pp. 13556-13569 ◽  
Author(s):  
Amanda R. Luu ◽  
Cara Wong ◽  
Vishal Agrawal ◽  
Nathan Wise ◽  
Britta Handyside ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Lysosomal Storage Disease ◽  
Storage Disease ◽  
Activity Levels ◽  
Multienzyme Complex ◽  
Lysosomal Storage ◽  
Gm1 Gangliosidosis ◽  
Enzyme Replacement ◽  
Clinical Onset

Mutations in the galactosidase β 1 (GLB1) gene cause lysosomal β-galactosidase (β-Gal) deficiency and clinical onset of the neurodegenerative lysosomal storage disease, GM1 gangliosidosis. β-Gal and neuraminidase 1 (NEU1) form a multienzyme complex in lysosomes along with the molecular chaperone, protective protein cathepsin A (PPCA). NEU1 is deficient in the neurodegenerative lysosomal storage disease sialidosis, and its targeting to and stability in lysosomes strictly depend on PPCA. In contrast, β-Gal only partially depends on PPCA, prompting us to investigate the role that β-Gal plays in the multienzyme complex. Here, we demonstrate that β-Gal negatively regulates NEU1 levels in lysosomes by competitively displacing this labile sialidase from PPCA. Chronic cellular uptake of purified recombinant human β-Gal (rhβ-Gal) or chronic lentiviral-mediated GLB1 overexpression in GM1 gangliosidosis patient fibroblasts coincides with profound secondary NEU1 deficiency. A regimen of intermittent enzyme replacement therapy dosing with rhβ-Gal, followed by enzyme withdrawal, is sufficient to augment β-Gal activity levels in GM1 gangliosidosis patient fibroblasts without promoting NEU1 deficiency. In the absence of β-Gal, NEU1 levels are elevated in the GM1 gangliosidosis mouse brain, which are restored to normal levels following weekly intracerebroventricular dosing with rhβ-Gal. Collectively, our results highlight the need to carefully titrate the dose and dosing frequency of β-Gal augmentation therapy for GM1 gangliosidosis. They further suggest that intermittent intracerebroventricular enzyme replacement therapy dosing with rhβ-Gal is a tunable approach that can safely augment β-Gal levels while maintaining NEU1 at physiological levels in the GM1 gangliosidosis brain.

scholarly journals Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease

2016 ◽  
Vol 24 (12) ◽  
pp. 2054-2063 ◽  
Author(s):  
Marialuisa Alliegro ◽  
Rita Ferla ◽  
Edoardo Nusco ◽  
Chiara De Leonibus ◽  
Carmine Settembre ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Lysosomal Storage Disease ◽  
Low Dose ◽  
Storage Disease ◽  
Lysosomal Storage ◽  
Enzyme Replacement

Is there a role for scintigraphic imaging of bone manifestations in Gaucher disease?

2008 ◽  
Vol 47 (06) ◽  
pp. 239-247 ◽  
Author(s):  
S. Kohlfürst ◽  
H. J. Gallowitsch ◽  
E. Kresnik ◽  
P. Lind ◽  
A. B. Mehta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lysosomal Storage Disease ◽  
Gaucher Disease ◽  
Storage Disease ◽  
Lysosomal Storage ◽  
Scintigraphic Imaging ◽  
Imaging Methods ◽  
X Ray ◽  
Deficient Activity

SummaryGaucher disease is the most prevalent inherited, lysosomal storage disease and is caused by deficient activity of the enzyme β-glucocerebrosidase. Bone and bone marrow alterations are frequent in the most prevalent non-neuronopathic form of Gaucher disease. Imaging of bone manifestations in Gaucher disease is performed by a variety of imaging methods, conventional X-ray and MRI as the most frequently and most important ones. However, different modalities of scintigraphic imaging have also been used. This article gives an overview on scintigraphic imaging with respect to bone manifestations in Gaucher disease discussing the advantages and limitations of scintigraphic imaging in comparison to other imaging methods.

Neonatal ascites due to lysosomal storage disease.

Radiology ◽  
1983 ◽  
Vol 149 (2) ◽  
pp. 463-467 ◽  
Author(s):  
A Daneman ◽  
D Stringer ◽  
B J Reilly
Keyword(s):  
Lysosomal Storage Disease ◽  
Storage Disease ◽  
Lysosomal Storage

scholarly journals Impairment of chaperone‐mediated autophagy leads to selective lysosomal degradation defects in the lysosomal storage disease cystinosis

2015 ◽  
Vol 7 (2) ◽  
pp. 158-174 ◽  
Author(s):  
Gennaro Napolitano ◽  
Jennifer L Johnson ◽  
Jing He ◽  
Celine J Rocca ◽  
Jlenia Monfregola ◽  
...  
Keyword(s):  
Lysosomal Storage Disease ◽  
Storage Disease ◽  
Lysosomal Storage ◽  
Lysosomal Degradation ◽  
Chaperone Mediated Autophagy
Sign in / Sign up

Export Citation Format

Share Document