Current and future therapies for Niemann–Pick C disease

Abstract

Introduction: Niemann–Pick disease type C (NPC) is caused by mutations in either of two genes, NPC1 or NPC2 which encode proteins involved in the regulation of normal intracellular lipid trafficking. The primary defect is affecting the cellular transport and/or processing of free cholesterol. The key laboratory diagnostic test for NPC is filipin staining of cultured skin fibroblasts from the patient, to demonstrate free cholesterol accumulation in lysosomes secondary to impaired intracellular cholesterol transport. Clinical presentations of NPC are extremely heterogeneous and clinical symptoms include progressive neurological deterioration and visceral organomegaly.

Areas covered: There is no curative treatment. Miglustat has been the only approved therapy for NPC disease. The efficacy of miglustat in patients with NPC has been demonstrated and recommendations to apply it have been published. The gastrointestinal adverse effects can be prevented by dose titration and dietary modifications.

Expert opinion: In the past decade, the approach in treating patients with NPC is based on reducing the synthesis of the stored substrate or combined therapies (e.g., miglustat, cyclodextrin and/or allopregnanalone), perhaps acting synergistically, have yielded the greatest increase in survivorship in NPC animals and can be a promise for treating patients still a definitive curative treatment appears.

Keywords::

• Niemann–Pick type C
• side effects
• substrate reduction therapy
• therapeutic options

Acknowledgments

To the Spanish Foundation of Niemann Pick disease for all their comments and collaboration treating these patients.

Notes

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