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
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 Npc1 nmf164 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 Npc1 nmf164 homozygous mice for weight, balance beam performance, or coat hanger performance. Interestingly, there was a trend to longer survival in the HPBCD-treated Npc1 nmf164 homozygous mice, which, when combined with the survival times of the saline-treated survivals (each of which was not different), became significant.
KeywordsNiemann-Pick C1 disease Hydroxypropyl-beta-cyclodextrin Nasal delivery Lung inflammation Neurodegeneration
We thank Maria Teresa Fiorenza for discussions and comments on the manuscript and Christina Marie Brentley and Yazmin Gonzales-Almazon for assistance.
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.
This work was supported in part by grant no. NIH NICHD R25HD080811 (F Ghishan/F Garcia/M Witte—multiple PIs).
Compliance with ethical standards
Conflict of interest
All authors declare no conflicts of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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