Gene therapy restores copper metabolism in mice model of Wilson diseasePublished: February 1, 2019
UPenn researchers have demonstrated the potential of adeno-associated virus-mediated gene therapy in providing long-term correction of copper metabolism in a clinically relevant animal model of Wilson disease.
Wilson’s disease (WD), also known as hepatolenticular degeneration, is a rare autosomal recessive genetic disorder caused by a mutation of the copper-transporting P-type ATPase (ATP7B) gene. It results in deleterious accumulation of copper in the liver and brain.
Current treatments are based on lifelong copper chelating drugs and zinc salts, which may cause side effects and do not restore normal copper metabolism. In the present study published in Human Gene Therapy Clinical Developments, Dr James Wilson and team at University of Pennsylvania assessed the efficacy of gene therapy to treat this condition using a mouse model of WD, the toxic milk mouse.
WD mice accumulated copper in the liver from birth and severe copper accumulation and concurrent liver disease were evident by two months of age. The team intravenously administered an adeno-associated viral (AAV) 8 vector expressing human ATP7B transgene into two-month-old WD mice. A significant reduction in liver copper levels was observed compared to age-matched, control WD mice and the effect was dose-dependent. Liver fibrosis completely disappeared in the mice injected with 1011 genome copies of AAV8 vector.
Thus, the data suggests AAV-mediated gene therapy as a promising approach for the long-term correction of copper metabolism in Wilson Disease and calls for further translational studies.
Source: A Gene Therapy Approach to Improve Copper Metabolism and Prevent Liver Damage in a Mouse Model of Wilson Disease. Greig J et al., Human Gene Therapy Clinical Development, January 2019. DOI