FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2799575045> ?p ?o ?g. }

• W2799575045 abstract "Niemann-Pick Type C (NP-C) is a lysosomal storage disorder with neurological and visceral pathology, for which there is currently no major disease modifying treatment. Loss of NPC1 function, a late endosomal transmembrane protein, leads to systemic intracellular lipid accumulation. The subsequent premature death is usually associated with neurological manifestations, such as neurodegeneration and neuroinflammation. This project focuses on the development and preclinical evaluation of gene therapy for NP-C in a mouse model using an adeno-associated viral (AAV) vector. The vector would be capable of delivering and expressing human NPC1 in the mouse brain and providing therapeutic benefit. AAV vectors exhibit efficient and widespread gene delivery throughout the brain, however their limited packaging capacity can be a constraint for larger genes. In this project extensive construct modifications were carried out to incorporate the relatively large NPC1 cDNA into a functional AAV serotype 9 vector, where NPC1 is controlled by a constitutively active neuronal promoter. Initial in vivo testing demonstrated successful NPC1 over-expression in administered mouse brains, compared to endogenous NPC1 levels in unadministered controls. No indications of toxicity were observed as a result of exogenous NPC1 overexpression in vivo. A series of preclinical proof of concept survival studies were subsequently carried out on the Npc1-/- model, where newborn Npc1-/- mice were administered with 4.6 x 109 vector genomes of AAV9-NPC1 via intracerebroventricular injections. Treated Npc1-/- mice exhibited an increased lifespan (median survival - 116.5 days) compared to untreated Npc1-/- mice (median survival - 75.5 days). Low dose treated mice exhibited permanent normalisation of locomotor function and significant neuronal rescue in all brain regions analysed. A subsequent study with a 65-fold dose increase resulted in an additional significant extension of lifespan, along with improved weight maintenance. Combined, these results demonstrate the potential beneficial use of gene therapy for NP-C and support the further development of this approach." @default.
• W2799575045 created "2018-05-17" @default.
• W2799575045 creator A5083414456 @default.
• W2799575045 date "2017-12-28" @default.
• W2799575045 modified "2023-09-23" @default.
• W2799575045 title "The development of gene therapy for Niemann-Pick Type C disease" @default.
• W2799575045 cites W104965598 @default.
• W2799575045 cites W114318986 @default.
• W2799575045 cites W1148361150 @default.
• W2799575045 cites W146706964 @default.
• W2799575045 cites W1485152739 @default.
• W2799575045 cites W1498704261 @default.
• W2799575045 cites W1509821238 @default.
• W2799575045 cites W1522504526 @default.
• W2799575045 cites W1537022954 @default.
• W2799575045 cites W1553052228 @default.
• W2799575045 cites W1564327509 @default.
• W2799575045 cites W1573172871 @default.
• W2799575045 cites W1574926840 @default.
• W2799575045 cites W1597721823 @default.
• W2799575045 cites W1599492633 @default.
• W2799575045 cites W1599588446 @default.
• W2799575045 cites W1605824081 @default.
• W2799575045 cites W1609953571 @default.
• W2799575045 cites W1623462303 @default.
• W2799575045 cites W1636792448 @default.
• W2799575045 cites W1697626716 @default.
• W2799575045 cites W170859630 @default.
• W2799575045 cites W172735993 @default.
• W2799575045 cites W1747355100 @default.
• W2799575045 cites W1769569140 @default.
• W2799575045 cites W1782667879 @default.
• W2799575045 cites W1793612594 @default.
• W2799575045 cites W1822742328 @default.
• W2799575045 cites W1825944839 @default.
• W2799575045 cites W1832822495 @default.
• W2799575045 cites W1835972708 @default.
• W2799575045 cites W1900339045 @default.
• W2799575045 cites W1907295175 @default.
• W2799575045 cites W1913924834 @default.
• W2799575045 cites W191504613 @default.
• W2799575045 cites W1960122038 @default.
• W2799575045 cites W1963623233 @default.
• W2799575045 cites W1964623101 @default.
• W2799575045 cites W1964935301 @default.
• W2799575045 cites W1965481483 @default.
• W2799575045 cites W1965696997 @default.
• W2799575045 cites W1966667764 @default.
• W2799575045 cites W1966923623 @default.
• W2799575045 cites W1967242914 @default.
• W2799575045 cites W1967516512 @default.
• W2799575045 cites W1967567480 @default.
• W2799575045 cites W1967750537 @default.
• W2799575045 cites W1967917811 @default.
• W2799575045 cites W1968713059 @default.
• W2799575045 cites W1970263992 @default.
• W2799575045 cites W1970997423 @default.
• W2799575045 cites W1971805725 @default.
• W2799575045 cites W1974030114 @default.
• W2799575045 cites W1974316422 @default.
• W2799575045 cites W1975248940 @default.
• W2799575045 cites W1976252335 @default.
• W2799575045 cites W1976329054 @default.
• W2799575045 cites W1976704599 @default.
• W2799575045 cites W1977239997 @default.
• W2799575045 cites W1977439828 @default.
• W2799575045 cites W1977451676 @default.
• W2799575045 cites W1978221944 @default.
• W2799575045 cites W1979195698 @default.
• W2799575045 cites W1979659851 @default.
• W2799575045 cites W1980020885 @default.
• W2799575045 cites W1980907251 @default.
• W2799575045 cites W1981497391 @default.
• W2799575045 cites W1981615019 @default.
• W2799575045 cites W1981632300 @default.
• W2799575045 cites W1981950767 @default.
• W2799575045 cites W1982347529 @default.
• W2799575045 cites W1983041761 @default.
• W2799575045 cites W1983330682 @default.
• W2799575045 cites W1983924189 @default.
• W2799575045 cites W1984325684 @default.
• W2799575045 cites W1984367585 @default.
• W2799575045 cites W1984983689 @default.
• W2799575045 cites W1985530230 @default.
• W2799575045 cites W1986816614 @default.
• W2799575045 cites W1986959907 @default.
• W2799575045 cites W1986980701 @default.
• W2799575045 cites W1987383217 @default.
• W2799575045 cites W1987704487 @default.
• W2799575045 cites W1988435252 @default.
• W2799575045 cites W1988513056 @default.
• W2799575045 cites W1988597220 @default.
• W2799575045 cites W1988681265 @default.
• W2799575045 cites W1989347025 @default.
• W2799575045 cites W1989674687 @default.
• W2799575045 cites W1990008286 @default.
• W2799575045 cites W1991105254 @default.
• W2799575045 cites W199204758 @default.
• W2799575045 cites W1992137530 @default.
• W2799575045 cites W1992203015 @default.

• next