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Study Data from Massachusetts General Hospital Update Understanding of Neuronal Ceroid Lipofuscinoses

June 26, 2014

By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Investigators publish new report on Neuronal Ceroid Lipofuscinoses. According to news originating from Boston, Massachusetts, by NewsRx correspondents, research stated, "Juvenile neuronal ceroid lipofuscinosis (JNCL or CLN3 disease) is an autosomal recessive lysosomal storage disease resulting from mutations in the CLN3 gene that encodes a lysosomal membrane protein. The disease primarily affects the brain with widespread intralysosomal accumulation of autofluorescent material and fibrillary gliosis, as well as the loss of specific neuronal populations."

Our news journalists obtained a quote from the research from Massachusetts General Hospital, "As an experimental treatment for the CNS manifestations of JNCL, we have developed a serotype rh.10 adeno-associated virus vector expressing the human CLN3 cDNA (AAVrh.10hCLN3). We hypothesized that administration of AAVrh.10hCLN3 to the Cln3(ex7/8) knock-in mouse model of JNCL would reverse the lysosomal storage defect, as well as have a therapeutic effect on gliosis and neuron loss. Newborn Cln3(ex7/8) mice were administered 3x10(10) genome copies of AAVrh.10hCLN3 to the brain, with control groups including untreated Cln3(ex7/8) mice and wild-type littermate mice. After 18 months, CLN3 transgene expression was detected in various locations throughout the brain, particularly in the hippocampus and deep anterior cortical regions. Changes in the CNS neuronal lysosomal accumulation of storage material were assessed by immunodetection of subunit C of ATP synthase, luxol fast blue staining, and periodic acid-Schiff staining. For all parameters, Cln3(ex7/8) mice exhibited abnormal lysosomal accumulation, but AAVrh.10hCLN3 administration resulted in significant reductions in storage material burden. There was also a significant decrease in gliosis in AAVrh.10hCLN3-treated Cln3(ex7/8) mice, and a trend toward improved neuron counts, compared with their untreated counterparts."

According to the news editors, the research concluded: "These data demonstrate that AAVrh.10 delivery of a wild-type cDNA to the CNS is not harmful and instead provides a partial correction of the neurological lysosomal storage defect of a disease caused by a lysosomal membrane protein, indicating that this may be an effective therapeutic strategy for JNCL and other diseases in this category."

For more information on this research see: Partial Correction of the CNS Lysosomal Storage Defect in a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis by Neonatal CNS Administration of an Adeno-Associated Virus Serotype rh. 10 Vector Expressing the Human CLN3 Gene. Human Gene Therapy, 2014;25(3):223-239. Human Gene Therapy can be contacted at: Mary Ann Liebert, Inc, 140 Huguenot Street, 3RD Fl, New Rochelle, NY 10801, USA. (Mary Ann Liebert, Inc. -; Human Gene Therapy -

The news correspondents report that additional information may be obtained from D. Sondhi, Massachusetts General Hospital, Center Human Genet Res, Boston, MA 02114, United States. Additional authors for this research include E.C. Scott, A. Chen, N.R. Hackett, A.M.S. Wong, A. Kubiak, H.R. Nelvagal, Y. Pearse, S.L. Cotman, J.D. Cooper and R.G. Crystal (see also Neuronal Ceroid Lipofuscinoses).

Keywords for this news article include: Biotechnology, Boston, Genetics, Virology, Gene Therapy, Massachusetts, United States, Bioengineering, Adeno-Associated Virus, North and Central America, Neuronal Ceroid Lipofuscinoses, Central Nervous System Diseases, Central Nervous System Infections

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Source: Gene Therapy Weekly

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