Early experience with compassionate use of 2 hydroxypropyl-beta-cyclodextrin for Niemann-Pick type C disease: review of initial published cases

Neurol Sci. 2017 May;38(5):727-743. doi: 10.1007/s10072-017-2833-9. Epub 2017 Feb 2.

Abstract

Niemann-Pick type C (NP-C) is a rare neurodegenerative disorder. Management is mainly supportive and symptomatic. The investigational use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a promising role in treating NP-C, although efficacy and safety have not been established. We conducted searches of MEDLINE, Cochrane, EMBASE, and other databases of reported cases of HP-β-CD compassionate use in NP-C disease. Sixteen reported cases were eligible, including evaluable information of 17 patients. The median onset age of HP-β-CD was 14 years (range 2-49 years). Intrathecal route was employed in 16 patients, in 3 patients simultaneously to IV infusions. Intracerebroventricular route was used in two patients. An objective improvement of clinical outcomes was measured in 14 patients, mainly by the NIH NP-C Clinical Severity Score and brainstem auditory evoked potential. Besides, an increase in metabolism and activities of the brain were observed in image tests and cholesterol biomarkers. Most patients showed some clinical benefit or a stabilization of NP-C progression. There were 17 adverse events (AEs) reported in 11 patients, 11 of them related to the drug and 6 to the route of administration. Loss of hearing was reported in four patients. The most severe AE were fever and chemical meningitis. Results suggest that efficacy may be partial and dependent on the early administration of the drug, the severity of the disease, and interpersonal variability. HP-β-CD could help stabilize NP-C with low toxicity potential, although some AEs have been reported. Moreover, controlled clinical trials would be necessary to evaluate the role of HP-β-CD in NP-C.

Keywords: 2-Hydroxypropyl-β-cyclodextrin; Effectiveness; Niemann–Pick; Toxicity.

Publication types

  • Review

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin / therapeutic use*
  • Databases, Bibliographic / statistics & numerical data
  • Excipients / therapeutic use*
  • Humans
  • Niemann-Pick Disease, Type C / drug therapy*

Substances

  • Excipients
  • 2-Hydroxypropyl-beta-cyclodextrin