FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3027540282> ?p ?o ?g. }

• W3027540282 endingPage "61" @default.
• W3027540282 startingPage "50" @default.
• W3027540282 abstract "Mucopolysaccharidosis type IVA (MPS IVA) is due to the deficiency of GALNS (N-acetylgalactosamine 6-sulfate sulfatase) and is characterized by systemic skeletal dysplasia. We have evaluated adeno-associated virus 8 (AAV8) vectors expressing different forms of human GALNS under a liver-specific promoter. The vectors were delivered intravenously into 4-week-old MPS IVA knockout (KO) and immune tolerant (MTOL) mice at a dose of 5 × 1013 genome copies (GC)/kg. These mice were monitored for 12 weeks post-injection. GALNS enzyme activity was elevated significantly in plasma of all treated mice at 2 weeks post-injection. The activity observed was 4- to 19-fold higher than that in wild-type mice and was maintained throughout the monitoring period. Treatment with AAV vectors resulted in a reduction of keratan sulfate (KS) levels in plasma to normal levels 2 weeks post-injection, which were maintained until necropsy. Both vectors reduced the storage in articular cartilage, ligaments, and meniscus surrounding articular cartilage and growth plate region as well as heart muscle and valves. Our results suggest that the continuous presence of high levels of circulating enzyme increases the penetration into bone and heart and reduces the KS level, thereby improving storage in these regions. The current data support a strategy for developing a novel treatment to address the bone and heart disease in MPS IVA using AAV gene therapy. Mucopolysaccharidosis type IVA (MPS IVA) is due to the deficiency of GALNS (N-acetylgalactosamine 6-sulfate sulfatase) and is characterized by systemic skeletal dysplasia. We have evaluated adeno-associated virus 8 (AAV8) vectors expressing different forms of human GALNS under a liver-specific promoter. The vectors were delivered intravenously into 4-week-old MPS IVA knockout (KO) and immune tolerant (MTOL) mice at a dose of 5 × 1013 genome copies (GC)/kg. These mice were monitored for 12 weeks post-injection. GALNS enzyme activity was elevated significantly in plasma of all treated mice at 2 weeks post-injection. The activity observed was 4- to 19-fold higher than that in wild-type mice and was maintained throughout the monitoring period. Treatment with AAV vectors resulted in a reduction of keratan sulfate (KS) levels in plasma to normal levels 2 weeks post-injection, which were maintained until necropsy. Both vectors reduced the storage in articular cartilage, ligaments, and meniscus surrounding articular cartilage and growth plate region as well as heart muscle and valves. Our results suggest that the continuous presence of high levels of circulating enzyme increases the penetration into bone and heart and reduces the KS level, thereby improving storage in these regions. The current data support a strategy for developing a novel treatment to address the bone and heart disease in MPS IVA using AAV gene therapy." @default.
• W3027540282 created "2020-05-29" @default.
• W3027540282 creator A5015754895 @default.
• W3027540282 creator A5037896874 @default.
• W3027540282 creator A5038816770 @default.
• W3027540282 creator A5043124146 @default.
• W3027540282 creator A5071597606 @default.
• W3027540282 creator A5078509604 @default.
• W3027540282 creator A5078910435 @default.
• W3027540282 date "2020-09-01" @default.
• W3027540282 modified "2023-10-15" @default.
• W3027540282 title "Liver-Targeted AAV8 Gene Therapy Ameliorates Skeletal and Cardiovascular Pathology in a Mucopolysaccharidosis IVA Murine Model" @default.
• W3027540282 cites W1493047535 @default.
• W3027540282 cites W1603932632 @default.
• W3027540282 cites W1678128979 @default.
• W3027540282 cites W1741064851 @default.
• W3027540282 cites W1750390936 @default.
• W3027540282 cites W1966557548 @default.
• W3027540282 cites W1968496156 @default.
• W3027540282 cites W1982253396 @default.
• W3027540282 cites W1985629718 @default.
• W3027540282 cites W1993774764 @default.
• W3027540282 cites W2011350479 @default.
• W3027540282 cites W2022413744 @default.
• W3027540282 cites W2022842718 @default.
• W3027540282 cites W2024575792 @default.
• W3027540282 cites W2026342372 @default.
• W3027540282 cites W2036877355 @default.
• W3027540282 cites W2045542783 @default.
• W3027540282 cites W2048487684 @default.
• W3027540282 cites W2055259915 @default.
• W3027540282 cites W2056744628 @default.
• W3027540282 cites W2060496255 @default.
• W3027540282 cites W2062611561 @default.
• W3027540282 cites W2070132388 @default.
• W3027540282 cites W2073739917 @default.
• W3027540282 cites W2075022977 @default.
• W3027540282 cites W2079361153 @default.
• W3027540282 cites W2084225245 @default.
• W3027540282 cites W2092849832 @default.
• W3027540282 cites W2095716298 @default.
• W3027540282 cites W2095949514 @default.
• W3027540282 cites W2100359543 @default.
• W3027540282 cites W2102486404 @default.
• W3027540282 cites W2102547112 @default.
• W3027540282 cites W2115563362 @default.
• W3027540282 cites W2127364492 @default.
• W3027540282 cites W2130563912 @default.
• W3027540282 cites W2134220455 @default.
• W3027540282 cites W2142213548 @default.
• W3027540282 cites W2143504385 @default.
• W3027540282 cites W2158749858 @default.
• W3027540282 cites W2161471693 @default.
• W3027540282 cites W2166401212 @default.
• W3027540282 cites W2169219209 @default.
• W3027540282 cites W2238575688 @default.
• W3027540282 cites W2332247814 @default.
• W3027540282 cites W2345446948 @default.
• W3027540282 cites W2434163946 @default.
• W3027540282 cites W2506376364 @default.
• W3027540282 cites W2513119362 @default.
• W3027540282 cites W2514953815 @default.
• W3027540282 cites W2521367895 @default.
• W3027540282 cites W2529215576 @default.
• W3027540282 cites W2530403529 @default.
• W3027540282 cites W2558797397 @default.
• W3027540282 cites W2593342263 @default.
• W3027540282 cites W2609494883 @default.
• W3027540282 cites W2791944595 @default.
• W3027540282 cites W2803183799 @default.
• W3027540282 cites W2804407043 @default.
• W3027540282 cites W2897078573 @default.
• W3027540282 cites W2912280590 @default.
• W3027540282 cites W2912843979 @default.
• W3027540282 cites W2940605611 @default.
• W3027540282 cites W4250446838 @default.
• W3027540282 cites W4299510155 @default.
• W3027540282 doi "https://doi.org/10.1016/j.omtm.2020.05.015" @default.
• W3027540282 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7301175" @default.
• W3027540282 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32577432" @default.
• W3027540282 hasPublicationYear "2020" @default.
• W3027540282 type Work @default.
• W3027540282 sameAs 3027540282 @default.
• W3027540282 citedByCount "14" @default.
• W3027540282 countsByYear W30275402822021 @default.
• W3027540282 countsByYear W30275402822022 @default.
• W3027540282 countsByYear W30275402822023 @default.
• W3027540282 crossrefType "journal-article" @default.
• W3027540282 hasAuthorship W3027540282A5015754895 @default.
• W3027540282 hasAuthorship W3027540282A5037896874 @default.
• W3027540282 hasAuthorship W3027540282A5038816770 @default.
• W3027540282 hasAuthorship W3027540282A5043124146 @default.
• W3027540282 hasAuthorship W3027540282A5071597606 @default.
• W3027540282 hasAuthorship W3027540282A5078509604 @default.
• W3027540282 hasAuthorship W3027540282A5078910435 @default.
• W3027540282 hasBestOaLocation W30275402821 @default.
• W3027540282 hasConcept C104317684 @default.
• W3027540282 hasConcept C105702510 @default.

• next