{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:41:47Z","timestamp":1791013307519,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,7,5]]},"abstract":"<jats:p>Tay-Sachs disease is a prototypic neurodegenerative disease. Lysosomal storage of GM2 ganglioside in Tay-Sachs and the related disorder, Sandhoff disease, is caused by deficiency of \u03b2-hexosaminidase A, a heterodimeric protein. Tay-Sachs-related diseases (GM2 gangliosidoses) are incurable, but gene therapy has the potential for widespread correction of the underlying lysosomal defect by means of the secretion-recapture cellular pathway for enzymatic complementation. Sandhoff mice, lacking the \u03b2-subunit of hexosaminidase, manifest many signs of classical human Tay-Sachs disease and, with an acute course, die before 20 weeks of age. We treated Sandhoff mice by stereotaxic intracranial inoculation of recombinant adeno-associated viral vectors encoding the complementing human \u03b2-hexosaminidase \u03b1 and \u03b2 subunit genes and elements, including an HIV tat sequence, to enhance protein expression and distribution. Animals survived for &gt;1 year with sustained, widespread, and abundant enzyme delivery in the nervous system. Onset of the disease was delayed with preservation of motor function; inflammation and GM2 ganglioside storage in the brain and spinal cord was reduced. Gene delivery of \u03b2-hexosaminidase A by using adeno-associated viral vectors has realistic potential for treating the human Tay-Sachs-related diseases.<\/jats:p>","DOI":"10.1073\/pnas.0603765103","type":"journal-article","created":{"date-parts":[[2006,6,26]],"date-time":"2006-06-26T20:53:55Z","timestamp":1151355235000},"page":"10373-10378","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":128,"title":["Effective gene therapy in an authentic model of Tay-Sachs-related diseases"],"prefix":"10.1073","volume":"103","author":[{"given":"M. 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