Benefit

Technology Description

Niemann-Pick disease type C (NPC) is an invariably fatal rare progressive genetic disorder which results in the inability of the body to transport cholesterol and other lipids within cells. This is caused by loss-of-function mutations in the NPC1 gene, and degradation of NPC1 protein. This leads to the accumulation of these fatty substances in tissues throughout the body, including the brain and liver, which inevitably leads to damage of the tissue. Most cases of NPC are detected during childhood and progress to life-threatening complications by midlife. There is currently no cure or treatment for NPC and novel gene therapies are needed to help patients affected by this genetic disorder. 

Dr. Schultz at the University of Iowa has developed a novel lipid-nanoparticle treatment to restore cellular NPC1 protein and improve trafficking. By improving and optimizing mRNA constructs of the NPC1 gene, Dr. Schultz has created a novel mRNA replacement therapy with improved NPC1 mRNA stability and increased protein expression. In vitro work has demonstrated these particles are able to completely restore NPC1 protein levels and improved processing and trafficking of the protein. In vivo work in a NPC mouse model shows a single peripheral administration improves liver NPC1 protein levels and secondary defects.  By relying on lipid-nanoparticles, this therapy is safer than other gene therapy techniques and have been shown to be well tolerated in human patients. This novel therapy offers a treatment for a disease in which none other exists, and the potential to significantly improve patients’ lives. 

UIRF Case No. 2023-071

Stage of Development

NPC1 mRNA lipid-nanoparticles have been tested in vitro using NPC1 deficient cell lines. On going work is partially completed using mouse models of Niemann-Pick C disease.