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Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease

Cain, Jacob T. et al.

Molecular therapy. Volume 27:Number 10 (2019, October 2nd); pp 1836-1847 -- Cell Press

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  • Title:
    Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease
  • Author: Cain, Jacob T.;
    Likhite, Shibi;
    White, Katherine A.;
    Timm, Derek J.;
    Davis, Samantha S.;
    Johnson, Tyler B.;
    Dennys-Rivers, Cassandra N.;
    Rinaldi, Federica;
    Motti, Dario;
    Corcoran, Sarah;
    Morales, Pablo;
    Pierson, Christopher;
    Hughes, Stephanie M.;
    Lee, Stella Y.;
    Kaspar, Brian K.;
    Meyer, Kathrin;
    Weimer, Jill M.
  • Found In: Molecular therapy. Volume 27:Number 10 (2019, October 2nd); pp 1836-1847
  • Journal Title: Molecular therapy
  • Subjects: Gene therapy--Periodicals; Molecular genetics--Periodicals; neuronal ceroid lipofuscinosis--neurodegenerative disease--gene rescue--adenovirus; Dewey: 615.89505
  • Rights: Licensed
  • Publication Details: Cell Press
  • Abstract: CLN6-Batten disease, a form of neuronal ceroid lipofuscinosis is a rare lysosomal storage disorder presenting with gradual declines in motor, visual, and cognitive abilities and early death by 12–15 years of age. We developed a self-complementary adeno-associated virus serotype 9 (scAAV9) vector expressing the human CLN6 gene under the control of a chicken β-actin (CB) hybrid promoter. Intrathecal delivery of scAAV9.CB.hCLN6 into the cerebrospinal fluid (CSF) of the lumbar spinal cord of 4-year-old non-human primates was safe, well tolerated, and led to efficient targeting throughout the brain and spinal cord. A single intracerebroventricular (i.c.v.) injection at post-natal day 1 in Cln6 mutant mice delivered scAAV9.CB.CLN6 directly into the CSF, and it prevented or drastically reduced all of the pathological hallmarks of Batten disease. Moreover, there were significant improvements in motor performance, learning and memory deficits, and survival in treated Cln6 mutant mice, extending survival from 15 months of age (untreated) to beyond 21 months of age (treated). Additionally, many parameters were similar to wild-type counterparts throughout the lifespan of the treated mice. Graphical Abstract CLN6-Batten disease is a fatal lysosomal storage disorder that primarily affects children. Weimer and colleagues developed an AAV9 gene therapy that was well tolerated in mice and non-human primates. Delivery of this therapy into the brain of CLN6-Batten mice prevented most neurodegenerative symptoms, with treated mice living a full lifespan.
  • Identifier: System Number: ETOCvdc_100089542555.0x000001; Journal ISSN: 1525-0016; 10.1016/j.ymthe.2019.06.015
  • Publication Date: 2019
  • Physical Description: Electronic
  • Shelfmark(s): 5900.856500
  • UIN: ETOCvdc_100089542555.0x000001

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