Lactosyl-β-cyclodextrin against Hepatomegaly in Niemann-Pick Type C Disease

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The first paper in the special issue of Nanomaterials “Nanoconstructs Based on Cyclodextrins” has been published.

Mono-lactosyl β-CD (mono-Lac-β-CD) diminished cholesterol accumulation as efficiently as HP-β-CD in model of NPC hepatocytes. A novel multi-lactosyl β-CD (Lac-β-CD) also showed cholesterol-lowering effect in NPC-like HepG2 cells.  In this paper the therapeutic effect of Lac-β-CD on hepatomegaly in the NPC model mice (Npc1−/− mice) was studied its safety in wild type (WT) mice was evaluated with the following experiments:

  • Liver accumulation was studied after subcutaneous administration of fluorescently-labeled Lac-β-CD and HP-β-CD to WT mice.
  • The effects of Lac-β-CD on vacuolar degeneration of the liver and on liver inflammation were examined.
  • Tissue cholesterol accumulation in Npc1−/− mice after single or weekly administration of Lac-β-CD was investigated.
  • Plasma biochemistry was analyzed.
  • Lung toxicity of high acute doses of Lac-β-CD and HP-β-CD in WT mice was measured.

The results suggested that Lac-β-CyD has great potential for safer and effective treatment of hepatomegaly in NPC:

  • Lac-β-CD significantly lowered free cholesterol levels in endolysosomes of hepatocytes and improved hepatomegaly in NPC model mice.
  • Even a high dose of Lac-β-CD did not show the side effects seen after HP-β-CyD administration .

Maeda, Y.; Motoyama, K.; Nishiyama, R.; Higashi, T.; Onodera, R.; Nakamura, H.; Takeo, T.; Nakagata, N.; Yamada, Y.; Ishitsuka, Y.; Kondo, Y.; Irie, T.; Era, T.; Arima, H. In vivo Efficacy and Safety Evaluation of Lactosyl-β-cyclodextrin as a Therapeutic Agent for Hepatomegaly in Niemann-Pick Type C Disease. Nanomaterials 2019, 9, 802.

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