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High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Quantification of Glycosaminoglycans as Biomarkers of Mucopolysaccharidosis II.
Wang, Junhua; Bhalla, Akhil; Ullman, Julie C; Fang, Meng; Ravi, Ritesh; Arguello, Annie; Thomsen, Elliot; Tsogtbaatar, Buyankhishig; Guo, Jing L; Skuja, Lukas L; Dugas, Jason C; Davis, Sonnet S; Poda, Suresh B; Gunasekaran, Kannan; Costanzo, Simona; Sweeney, Zachary K; Henry, Anastasia G; Harris, Jeffrey M; Henne, Kirk R; Astarita, Giuseppe.
Afiliación
  • Wang J; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Bhalla A; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Ullman JC; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Fang M; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Ravi R; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Arguello A; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Thomsen E; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Tsogtbaatar B; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Guo JL; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Skuja LL; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Dugas JC; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Davis SS; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Poda SB; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Gunasekaran K; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Costanzo S; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Sweeney ZK; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Henry AG; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Harris JM; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Henne KR; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
  • Astarita G; Denali Therapeutics, Inc., 161 Oyster Point Blvd, South San Francisco, CA 94080, USA.
Int J Mol Sci ; 21(15)2020 Jul 30.
Article en En | MEDLINE | ID: mdl-32751752
We recently developed a blood-brain barrier (BBB)-penetrating enzyme transport vehicle (ETV) fused to the lysosomal enzyme iduronate 2-sulfatase (ETV:IDS) and demonstrated its ability to reduce glycosaminoglycan (GAG) accumulation in the brains of a mouse model of mucopolysaccharidosis (MPS) II. To accurately quantify GAGs, we developed a plate-based high-throughput enzymatic digestion assay coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to simultaneously measure heparan sulfate and dermatan sulfate derived disaccharides in tissue, cerebrospinal fluid (CSF) and individual cell populations isolated from mouse brain. The method offers ultra-high sensitivity enabling quantitation of specific GAG species in as low as 100,000 isolated neurons and a low volume of CSF. With an LOD at 3 ng/mL and LLOQs at 5-10 ng/mL, this method is at least five times more sensitive than previously reported approaches. Our analysis demonstrated that the accumulation of CSF and brain GAGs are in good correlation, supporting the potential use of CSF GAGs as a surrogate biomarker for brain GAGs. The bioanalytical method was qualified through the generation of standard curves in matrix for preclinical studies of CSF, demonstrating the feasibility of this assay for evaluating therapeutic effects of ETV:IDS in future studies and applications in a wide variety of MPS disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores / Mucopolisacaridosis II / Glicosaminoglicanos / Iduronato Sulfatasa Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores / Mucopolisacaridosis II / Glicosaminoglicanos / Iduronato Sulfatasa Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza