scholarly journals A canine model for neuronal ceroid lipofuscinosis highlights the promise of gene therapy for lysosomal storage diseases

2016 ◽  
Vol 4 (S1) ◽  
pp. S20-S20
Author(s):  
Jonathan E. Phillips ◽  
Richard H. Gomer
Keyword(s):  
Gene Therapy ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Lysosomal Storage Diseases ◽  
Canine Model ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Ceroid Lipofuscinosis

scholarly journals Multiplex Tandem Mass Spectrometry Enzymatic Activity Assay for Newborn Screening of the Mucopolysaccharidoses and Type 2 Neuronal Ceroid Lipofuscinosis

2017 ◽  
Vol 63 (6) ◽  
pp. 1118-1126 ◽  
Author(s):  
Yang Liu ◽  
Fan Yi ◽  
Arun Babu Kumar ◽  
Naveen Kumar Chennamaneni ◽  
Xinying Hong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Lysosomal Storage Diseases ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Ceroid Lipofuscinosis

Abstract BACKGROUND We expanded the use of tandem mass spectrometry combined with liquid chromatography (LC-MS/MS) for multiplex newborn screening of seven lysosomal enzymes in dried blood spots (DBS). The new assays are for enzymes responsible for the mucopolysaccharidoses (MPS-I, -II, -IIIB, -IVA, -VI, and -VII) and type 2 neuronal ceroid lipofuscinosis (LINCL). METHODS New substrates were prepared and characterized for tripeptidyl peptidase 1 (TPP1), α-N-acetylglucosaminidase (NAGLU), and lysosomal β-glucuronidase (GUSB). These assays were combined with previously developed assays to provide a multiplex LC-MS/MS assay of 7 lysosomal storage diseases. Multiple reaction monitoring of ion dissociations for enzyme products and deuterium-labeled internal standards was used to quantify the enzyme activities. RESULTS Deidentified DBS samples from 62 nonaffected newborns were analyzed to simultaneously determine (run time 2 min per DBS) the activities of TPP1, NAGLU, and GUSB, along with those for α-iduronidase (IDUA), iduronate-2-sulfatase (I2S), N-acetylgalactosamine-6-sulfatase (GALNS), and N-acetylgalactosamine-4-sulfatase (ARSB). The activities measured in the 7-plex format showed assay response-to-blank-activity ratios (analytical ranges) of 102–909 that clearly separated healthy infants from affected children. CONCLUSIONS The new multiplex assay provides a robust comprehensive newborn screening assay for the mucopolysaccharidoses. The method has been expanded to include additional lysosomal storage diseases.

Clinical Development of Cell Therapies to Halt Lysosomal Storage Diseases: Results and Lessons Learned

2021 ◽  
Vol 21 ◽  
Author(s):  
Valeria Graceffa
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Ex Vivo ◽  
Gene Transfection ◽  
Lysosomal Storage Diseases ◽  
Lessons Learned ◽  
Brain Targeting ◽  
Lysosomal Storage ◽  
Cell Therapies ◽  
Storage Diseases

: Although cross-correction was discovered more than 50 years ago, and held the promise of drastically improving disease management, still no cure exists for lysosomal storage diseases (LSDs). Cell therapies hold the potential to halt disease progression: either a subset of autologous cells can be ex vivo/ in vivo transfected with the functional gene or allogenic wild type stem cells can be transplanted. However, majority of cell-based attempts have been ineffective, due to the difficulties in reversing neuronal symptomatology, in finding appropriate gene transfection approaches, in inducing immune tolerance, reducing the risk of graft versus host disease (GVHD) when allogenic cells are used and that of immune response when engineered viruses are administered, coupled with a limited secretion and uptake of some enzymes. In the last decade, due to advances in our understanding of lysosomal biology and mechanisms of cross-correction, coupled with progresses in gene therapy, ongoing pre-clinical and clinical investigations have remarkably increased. Even gene editing approaches are currently under clinical experimentation. This review proposes to critically discuss and compare trends and advances in cell-based and gene therapy for LSDs. Systemic gene delivery and transplantation of allogenic stem cells will be initially discussed, whereas proposed brain targeting methods will be then critically outlined.

Sign in / Sign up

Export Citation Format

Share Document