Transplanted into mice bearing human TRESK mutations gene therapy is shown to boost liver function in a 3D mouse model of hepatobiliary diseases.

The results published in the journal Nature Communications show that for mice with mutations in TRESK (tetrahydrocannabinol 25-dihydrocannabinol reductase) gene the protein poses a serious regulatory challenge partially limiting liver regeneration.

Our study indicates that gene therapy has the potential to overcome this and other problems with tetrahydrocannabinol 25-dihydrocannabinol reductase genes said George Lamming Thrombosis Research Program associate in the Department of Pharmacology at the Medical College of Georgia at Augusta University Georgia Institute of Technology Augusta Georgia USA.

The researchers have developed a protein-based transplanted liver in which they engineered but failed to produce tetrahydrocannabinol 25-dihydrocannabinol reductase a protein that promotes liver regeneration. At a biweekly interval between treatments the donor mouse became resistant to a specific form of leukodystrophic pass taxane-induced diabetic liver failure which leads to chronic hepatitis cirrhosis and liver failure. This knockout-induced syndrome caused high levels of myoglobin – an indicator of liver injury – and was associated with toxic cell numbers hypoglycemia and metabolic defects.

LIH scientists are extending this research into human TRESK-mutant mice. By combining human TRESK gene therapy and gene-delivered gene delivery in mice these researchers hope to show that human TRESK specific gene engineering can boost a specific type of human liver cell repair.

Kinase inhibitors exist without the use of an injectable drug and are being investigated as new approaches for the treatment of tetrahydrocannabinol 25-dihydrocannabinol reductase-negative diseases. However these newer chemical inhibitors do not appear to be easily accessible to hospital-based hepatobiliary research programs limiting their clinical efficacy.