Reversal of pathology in the entire brain of mucopolysaccharidosis type VII mice after lentivirus-mediated gene transfer

A. Bosch, E. Perret, N. Desmaris, D. Trono, J.M. Heard

Research output: Contribution to journalArticleResearchpeer-review

121 Citations (Scopus)

Abstract

Gene transfer vectors derived from human immunodeficiency virus (HIV-1) efficiently transduce nondividing cells and remain stably integrated in their genome. Long-term expression of reporter genes has been documented after intracerebral injection of these vectors. Using a HIV-based vector, we looked for a reversal of brain damage in the beta-glucuronidase-deficient mucopolysaccharidosis type VII mouse, an animal model. of human lysosomal storage diseases. The vector suspension was injected stereotactically in the brain of 10-week-old animals, an age at which storage lesions are patent in glia, perivascular cells, and neurons. Either a single intrastriatal injection or multiple injections in both cerebral hemispheres and in the cerebellum mere performed. Local tolerance, enzyme delivery, and correction of storage lesions were investigated by comprehensive analysis of serial sections of the entire brain of mice killed 6 or 16 weeks postinjection, Histochemical staining detected enzyme activity in widely distributed areas, the size of which increased with time. Clearance of lysosomal storage extended far beyond enzyme-positive areas. In mice receiving multiple injections of the vector, complete correction or significant reduction of the pathology was observed in every section, suggesting disease regression in the entire brain. These results may have implications for the treatment of neurological symptoms in lysosomal storage diseases.
Original languageEnglish
Pages (from-to)1139-1150
JournalHuman Gene Therapy
Volume11
Issue number8
Publication statusPublished - 1 Jan 2000

Fingerprint

Dive into the research topics of 'Reversal of pathology in the entire brain of mucopolysaccharidosis type VII mice after lentivirus-mediated gene transfer'. Together they form a unique fingerprint.

Cite this