Decreased neural stem cell proliferation and olfaction in mouse models of Niemann–Pick C1 disease and the response to hydroxypropyl-β-cyclodextrin

Jessica Dragotto, Giampiero Palladino, Sonia Canterini, Paola Caporali, Rutaraj Patil, Maria Teresa Fiorenza, Robert P. Erickson

Research output: Contribution to journalArticlepeer-review


The Npc1nih/nih-null model and the Npc1nmf164/nmf164 hypomorph models of Niemann–Pick C1 (NPC1) disease show defects in olfaction. We have tested the effects of the life-prolonging treatment hydroxypropyl-beta-cyclodextrin (HPBCD) on olfaction and neural stem cell numbers when delivered either systemically or by nasal inhalation. Using the paradigm of finding a hidden cube of food after overnight food deprivation, Npc1nih/nih homozygous mice showed a highly significant delay in finding the food compared with wild-type mice. Npc1nmf164/nmf164 homozygous mice showed an early loss of olfaction which was mildly corrected by somatic delivery of HPBCD which also increased the number of neural stem cells in the mutant but did not change the number in wild-type mice. In contrast, nasal delivery of this drug, at 1/5 the dosage used for somatic delivery, to Npc1nmf164/nmf164 mutant mice delayed loss of olfaction but the control of nasal delivered saline did so as well. The nasal delivery of HPBCD to wild-type mice caused loss of olfaction but nasal delivery of saline did not. Neural stem cell counts were not improved by nasal therapy with HPBCD. We credit the delay in olfaction found with the treatment, a delay which was also found for time of death, to a large amount of stimulation the mice received with handling during the nasal delivery.

Original languageEnglish
JournalJournal of Applied Genetics
Publication statusAccepted/In press - Jan 1 2019


  • Hydroxypropyl-beta-cyclodextrins
  • Nasal delivery
  • Neural stem cells
  • Niemann–Pick C1 disease
  • Olfaction

ASJC Scopus subject areas

  • Genetics


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