Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration

Daniel A. Wolf; Leah R. Hanson; Elena L. Aronovich; Zhenhong Nan; Walter C. Low; William H. Frey; R. Scott McIvor

doi:10.1016/j.ymgme.2012.02.006

Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration

Daniel A. Wolf, Leah R. Hanson, Elena L. Aronovich, Zhenhong Nan, Walter C. Low, William H. Frey, R. Scott McIvor

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

Here we provide the first evidence that therapeutic levels of a lysosomal enzyme can bypass the blood-brain barrier following intranasal administration α-l-iduronidase (IDUA) activity was detected throughout the brains of IDUA-deficient mice following a single intranasal treatment with concentrated Aldurazyme® (laronidase) and was also detected after intranasal treatment with an adeno-associated virus (AAV) vector expressing human IDUA. These results suggest that intranasal routes of delivery may be efficacious in the treatment of lysosomal storage disorders.

Original language	English (US)
Pages (from-to)	131-134
Number of pages	4
Journal	Molecular Genetics and Metabolism
Volume	106
Issue number	1
DOIs	https://doi.org/10.1016/j.ymgme.2012.02.006
State	Published - May 2012

Bibliographical note

Funding Information:
We would like to thank B. Koniar for excellent animal care. This work was supported by NIH grants P01HD032652 (RSM), 1R01DK082516 (Dr. Perry Hackett), and training grant T32 DA022616-01 (DAW).

Keywords

Adeno-associated virus
Alpha-l-iduronidase
Blood-brain barrier
Intranasal delivery
Mucopolysaccharidosis
Neurological disease

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10.1016/j.ymgme.2012.02.006

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title = "Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration",

abstract = "Here we provide the first evidence that therapeutic levels of a lysosomal enzyme can bypass the blood-brain barrier following intranasal administration α-l-iduronidase (IDUA) activity was detected throughout the brains of IDUA-deficient mice following a single intranasal treatment with concentrated Aldurazyme{\textregistered} (laronidase) and was also detected after intranasal treatment with an adeno-associated virus (AAV) vector expressing human IDUA. These results suggest that intranasal routes of delivery may be efficacious in the treatment of lysosomal storage disorders.",

keywords = "Adeno-associated virus, Alpha-l-iduronidase, Blood-brain barrier, Intranasal delivery, Mucopolysaccharidosis, Neurological disease",

author = "Wolf, {Daniel A.} and Hanson, {Leah R.} and Aronovich, {Elena L.} and Zhenhong Nan and Low, {Walter C.} and Frey, {William H.} and McIvor, {R. Scott}",

note = "Funding Information: We would like to thank B. Koniar for excellent animal care. This work was supported by NIH grants P01HD032652 (RSM), 1R01DK082516 (Dr. Perry Hackett), and training grant T32 DA022616-01 (DAW).",

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doi = "10.1016/j.ymgme.2012.02.006",

language = "English (US)",

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pages = "131--134",

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AU - Wolf, Daniel A.

AU - Hanson, Leah R.

AU - Aronovich, Elena L.

AU - Nan, Zhenhong

AU - Low, Walter C.

AU - Frey, William H.

AU - McIvor, R. Scott

N1 - Funding Information: We would like to thank B. Koniar for excellent animal care. This work was supported by NIH grants P01HD032652 (RSM), 1R01DK082516 (Dr. Perry Hackett), and training grant T32 DA022616-01 (DAW).

PY - 2012/5

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N2 - Here we provide the first evidence that therapeutic levels of a lysosomal enzyme can bypass the blood-brain barrier following intranasal administration α-l-iduronidase (IDUA) activity was detected throughout the brains of IDUA-deficient mice following a single intranasal treatment with concentrated Aldurazyme® (laronidase) and was also detected after intranasal treatment with an adeno-associated virus (AAV) vector expressing human IDUA. These results suggest that intranasal routes of delivery may be efficacious in the treatment of lysosomal storage disorders.

AB - Here we provide the first evidence that therapeutic levels of a lysosomal enzyme can bypass the blood-brain barrier following intranasal administration α-l-iduronidase (IDUA) activity was detected throughout the brains of IDUA-deficient mice following a single intranasal treatment with concentrated Aldurazyme® (laronidase) and was also detected after intranasal treatment with an adeno-associated virus (AAV) vector expressing human IDUA. These results suggest that intranasal routes of delivery may be efficacious in the treatment of lysosomal storage disorders.

KW - Adeno-associated virus

KW - Alpha-l-iduronidase

KW - Blood-brain barrier

KW - Intranasal delivery

KW - Mucopolysaccharidosis

KW - Neurological disease

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SN - 1096-7192

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Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration

Abstract

Bibliographical note

Keywords

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