Acid sphingomyelinase deficient mice: a model of types A and B Niemann–Pick disease
Analysis of the ASM deficient mice showed their tissues had no detectable ASM activity, the blood cholesterol levels and sphingomyelin in the liver and brain were elevated, and atrophy of the cerebellum and marked deficiency of Purkinje cells was evident.
siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury.
- B. Molitoris, P. Dagher, E. Feinstein
- Biology, ChemistryJournal of the American Society of Nephrology
- 1 August 2009
Data indicate that rapid delivery of siRNA to proximal tubule cells follows intravenous administration, suggesting potential therapeutic benefit for ischemic and nephrotoxic kidney injury.
Toxicological and pharmacokinetic properties of chemically modified siRNAs targeting p53 RNA following intravenous administration.
Clinical testing of intravenous administration of I5NP for the preservation of renal function following acute ischemia/reperfusion injury supported by toxicological and pharmacokinetic properties reported.
Hematopoietic stem cell gene therapy leads to marked visceral organ improvements and a delayed onset of neurological abnormalities in the acid sphingomyelinase deficient mouse model of Niemann–Pick…
- S. Miranda, S. Erlich, V. Friedrich, S. Gatt, E. Schuchman
- Biology, MedicineGene Therapy
- 1 October 2000
Results indicated that hematopoietic stem cell gene therapy should be effective for the treatment of non-neurological type B NPD, but improved techniques for targeting the transplanted cells and/or expressed enzyme to specific sites of pathology in the central nervous system must be developed in order to achieve effective treatment for type A NPD.
Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study).
Phase 1 dose-escalation study of a siRNA targeting the RTP801 gene in age-related macular degeneration patients
A single IVT injection of PF-0523655 ≤3000 μg seems safe and well tolerated in eyes with neovascular AMD.
Safety and Tolerability Study of an Intravenously Administered Small Interfering Ribonucleic Acid (siRNA) Post On-Pump Cardiothoracic Surgery in Patients at Risk of Acute Kidney Injury
Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study).
- Q. Nguyen, R. Schachar, S. Erlich
- MedicineInvestigative Ophthalmology and Visual Science
- 15 November 2012
PF-04523655 showed a dose-related tendency for improvement in BCVA in DME patients, and may offer a new mode of therapeutic action in the management of DME.
Biochemical, pathological, and clinical response to transplantation of normal bone marrow cells into acid sphingomyelinase-deficient mice.
- S. Miranda, S. Erlich, V. Friedrich, M. Haskins, S. Gatt, E. Schuchman
- Medicine, BiologyTransplantation
- 15 April 1998
Results demonstrated that BMT could alter the pathologic phenotype in ASMKO mice, but that this procedure alone was not sufficient to elicit a complete therapeutic effect.
Fluorescence-based selection of gene-corrected hematopoietic stem and progenitor cells from acid sphingomyelinase-deficient mice: implications for Niemann-Pick disease gene therapy and the…
The methods described within this manuscript are particularly useful for evaluating hematopoietic stem cell gene transfer in vivo because the marker gene used in the procedure (ASM) encodes a naturally occurring mammalian enzyme that has no known adverse effects, and the fluorescent compound used for selection is removed from the cells before transplantation.