Somatic gene therapy of diseases associated with metal accumulation, e.g. Wilson's, Menkes' and Alzheimer's disease, comprises using a gene under the control of a metal-responsive promoter

摘要

Somatic gene therapy that uses a metal-sensitive promoter, e.g. the metallothionein-I promoter (P), for treating diseases that are accompanied by metal accumulation, particularly of copper in Wilson's and Alzheimer's diseases, is new. Independent claims are also included for: (1) a copper/zinc-inducible Wilson gene (ATP7B)/adeno associated virus (AAV) construct for somatic therapy of Wilson's disease; (2) a small version (P') of (P) that is fully functional in size-limited vectors; (3) a small version (A) of the human ATP7B cDNA, lacking the first two copper-binding sites, that is fully functional; (4) a combination (X) of (P') and (A), plus a polyadenylation signal and two terminal repeats of AAV, forming a 5.1 kb inducible ATP7B gene construct which, when packaged in an AAV system, makes possible somatic gene therapy of Wilson's disease; (5) somatic gene therapy using (P) or (P') to induce gene expression after administration of zinc, e.g. oral or intravenous zinc substitution; (6) similar somatic gene therapy of Menkes' disease, using the ATP7A gene, lacking the first two copper-binding sites; and (7) a kit for diagnosing Wilson's or Menkes' disease from a blood sample.