Early experience with compassionate use of 2 hydroxypropyl-beta-cyclodextrin for Niemann-Pick type C disease: review of initial published cases.
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.
Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Juan Eduardo
JE
Megías-Vericat
Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Ana
A
García-Robles
Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain. company_mjoalb@gva.es.
María José
MJ
Company-Albir
Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
María José
MJ
Fernández-Megía
Unidad Mixta de Esclerosis Múltiple y Neurorregeneración, IIS Hospital La Fe, Universitat de València, Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Francisco Carlos
FC
Pérez-Miralles
Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Eduardo
E
López-Briz
Unidad Mixta de Esclerosis Múltiple y Neurorregeneración, IIS Hospital La Fe, Universitat de València, Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Bonaventura
B
Casanova
Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
José Luis
JL
Poveda
D000073738:2-Hydroxypropyl-beta-cyclodextrin / Q000627:therapeutic use*; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D005079:Excipients / Q000627:therapeutic use*; D006801:Humans; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy*
D005079:Excipients; D000073738:2-Hydroxypropyl-beta-cyclodextrin
2-Hydroxypropyl-β-cyclodextrin; Effectiveness; Niemann–Pick; Toxicity