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A pilot study of direct delivery of hydroxypropyl-beta-cyclodextrin to the lung by the nasal route in a mouse model of Niemann-Pick C1 disease: motor performance is unaltered and lung disease is worsened

  • Human Genetics • Short Communication
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Abstract

We have tested the efficacy of hydroxypropyl-beta-cyclodextrin (HPBCD) delivered by the nasal route in the mouse model of juvenile Niemann-Pick C1 disease (NPC1), as pulmonary disease has not responded to systemic therapy with this drug. Since mice have no gag reflex, coating of the nasal cavity, with possible access to the brain, would be followed by delivery of HPBCD to the lung. While foamy macrophages, containing stored cholesterol, were found in the Npc1nmf164 homozygous mice, a marked inflammatory response was found with inhaled HPBCD, both in mutant and wild-type animals. Slight inflammation also occasionally occurred with saline inhalation. There was no difference between the saline-treated, HPBCD-treated, and untreated Npc1nmf164 homozygous mice for weight, balance beam performance, or coat hanger performance. Interestingly, there was a trend to longer survival in the HPBCD-treated Npc1nmf164 homozygous mice, which, when combined with the survival times of the saline-treated survivals (each of which was not different), became significant.

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Acknowledgements

We thank Maria Teresa Fiorenza for discussions and comments on the manuscript and Christina Marie Brentley and Yazmin Gonzales-Almazon for assistance.

Funding

This work was supported in part by grant no. NIH NICHD R25HD080811 (F Ghishan/F Garcia/M Witte—multiple PIs).

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Authors and Affiliations

  1. Department of Pediatrics, University of Arizona College of Medicine, Tucson, AZ, USA

    Robert P. Erickson & Ruturaj Patil

  2. Department of Pathology, Seattle Children’s Hospital, University of Washington School of Medicine, Seattle, WA, USA

    Gail Deutsch

Authors
  1. Robert P. Erickson
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  2. Gail Deutsch
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  3. Ruturaj Patil
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Contributions

Robert P. Erickson designed and participated in the experiments and authored the manuscript. Gail Deutsch performed the histological examinations and corrected the manuscript. Rutaraj Patil performed experiments and data analysis.

Corresponding author

Correspondence to Robert P. Erickson.

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Conflict of interest

All authors declare no conflicts of interest.

Ethics approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Communicated by: Communicated by: Michal Witt

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Erickson, R.P., Deutsch, G. & Patil, R. A pilot study of direct delivery of hydroxypropyl-beta-cyclodextrin to the lung by the nasal route in a mouse model of Niemann-Pick C1 disease: motor performance is unaltered and lung disease is worsened. J Appl Genetics 59, 187–191 (2018). https://doi.org/10.1007/s13353-018-0431-z

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  • DOI: https://doi.org/10.1007/s13353-018-0431-z

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