Use of 2 hydroxypropyl-beta-cyclodextrin therapy in two adult Niemann Pick Type C patients

García-Robles, Ana; Company-Albir, María José; Megías‐Vericat, Juan Eduardo; Fernández-Megía, María José; Pérez‐Miralles, Francisco; López-Briz, Eduardo; Alcalá-Vicente, Carmen; Galeano, Inma; Casanova, Bonaventura; Poveda, José Luís

doi:10.1016/j.jns.2016.04.048

Cited by 18 publications

(23 citation statements)

References 13 publications

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“…The employment of HP-β-CD in adult-onset NPD-C has been described with variable results in two publications [48,49]. Sakiyama et al reported the IT treatment (VTS-270) of two adult patients of 37 and 28 years with doses from 100 to 400 mg every month.…”

Section: Experience In Humans: Efficacy Of the Intrathecal Administramentioning

confidence: 99%

“…The other patient suffered two episodes of toxic meningitis as well as worsening respiratory symptoms and swallow. After second chemical meningitis and neurologic progression of the disease, HP-β-CD treatment was discontinued [49].…”

Section: Experience In Humans: Efficacy Of the Intrathecal Administramentioning

confidence: 99%

“…Of the 17 AEs reported, 6 were related to the route of administration, specifically with the IT and ICV routes and 10 of them could be attributed by HP-β-CD. Six AEs associated to the route were: CNS bleed related to insertion of the Ommaya reservoir system in a patient treated with ICV HP-β-CD led to ICV administration suspended [34]; post lumbar puncture headache and vomiting resolved with switching a Whitacre spinal needles [41][42][43]; post lumbar puncture pain, headache, nausea, and vomiting resolved with symptomatic and postural treatment [44]; seizures with fever resolved without changes in treatment [40] and aspiration pneumonia; febrile syndrome; and candidiasis resolved with antibiotic and antifungal treatment [49].…”

Section: Experience In Humans: Potential Toxicities Of the Different mentioning

confidence: 99%

“…Four patients suffered from fever two or more times after HP-β-CD administrations [37,40,46,49]. In one case, fever was accompanied by seizures [40], whereas another patient showed an infusion reaction with fever and transient diffuse pulmonary cloudiness [37].…”

Section: Experience In Humans: Potential Toxicities Of the Different mentioning

confidence: 99%

“…The IT-OR was withdrawn, and HP-β-CD was reintroduced 2 months later because the patient's condition worsened [46]. Other patient showed two episodes of chemical meningitis (bacterial meningitis was discarded in both cases) after IT and IT-OR HP-β-CD administrations, although both were resolved quickly and without consequences [49]. This AE could be related to the method of administration or disease symptoms and not to HP-β-CD.…”

Section: Experience In Humans: Potential Toxicities Of the Different mentioning

confidence: 99%

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Use of 2-Hydroxypropyl-Beta-Cyclodextrin for Niemann-Pick Type C Disease

Megías‐Vericat¹,

Company-Albir²,

García-Robles³

et al. 2018

Cyclodextrin - A Versatile Ingredient

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Niemann-Pick disease type C (NPD-C) is a rare neurodegenerative disorder characterized by a lysosomal storage disorder. Treatment has been supportive and symptomatic. In animal studies, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a significant decrease in cerebellar damage, neurological progression, and higher lifespan. Based on these results, HP-β-CD has been tested in NPD-C patients for last 8 years. The first compassionate uses of intravenous HP-β-CD obtained a limited improvement in neurological symptoms, probably associated to the non-permeation of the blood-brain barrier. The change or combination with intrathecal administrations of HP-β-CD achieved higher benefits, especially improvement or stabilization of NPD-C progression. Biomarkers of neurological cholesterol homeostasis are being investigated in order to quantify the response of HP-β-CD treatment. The results of a clinical trial recently published have reproduced the slowing of NPD-C progression in 14 patients treated with a dose-escalation protocol of HP-β-CD intrathecal monthly infusions, with respect to a historical comparison cohort. The safety profile of this therapy is acceptable, being the loss of hearing as the most frequent adverse event. However, some severe toxicities have been reported in relation with HP-β-CD, including chemical meningitis and fever. The short experience with HP-β-CD suggested that it could be effective in the management of NPD-C.

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Section: Experience In Humans: Efficacy Of the Intrathecal Administramentioning

confidence: 99%

Section: Experience In Humans: Efficacy Of the Intrathecal Administramentioning

confidence: 99%

Section: Experience In Humans: Potential Toxicities Of the Different mentioning

confidence: 99%

Section: Experience In Humans: Potential Toxicities Of the Different mentioning

confidence: 99%

Section: Experience In Humans: Potential Toxicities Of the Different mentioning

confidence: 99%

See 3 more Smart Citations

Use of 2-Hydroxypropyl-Beta-Cyclodextrin for Niemann-Pick Type C Disease

Megías‐Vericat¹,

Company-Albir²,

García-Robles³

et al. 2018

Cyclodextrin - A Versatile Ingredient

Self Cite

View full text Add to dashboard Cite

show abstract

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

et al. 2017

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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.

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Small molecules as therapeutic agents for inborn errors of metabolism

Matalonga¹,

Gort

Ribes³

2016

J of Inher Metab Disea

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Most inborn errors of metabolism (IEM) remain without effective treatment mainly due to the incapacity of conventional therapeutic approaches to target the neurological symptomatology and to ameliorate the multisystemic involvement frequently observed in these patients. However, in recent years, the therapeutic use of small molecules has emerged as a promising approach for treating this heterogeneous group of disorders. In this review, we focus on the use of therapeutically active small molecules to treat IEM, including readthrough agents, pharmacological chaperones, proteostasis regulators, substrate inhibitors, and autophagy inducers. The small molecules reviewed herein act at different cellular levels, and this knowledge provides new tools to set up innovative treatment approaches for particular IEM. We review the molecular mechanism underlying therapeutic properties of small molecules, methodologies used to screen for these compounds, and their applicability in preclinical and clinical practice.

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Use of 2 hydroxypropyl-beta-cyclodextrin therapy in two adult Niemann Pick Type C patients

Cited by 18 publications

References 13 publications

Use of 2-Hydroxypropyl-Beta-Cyclodextrin for Niemann-Pick Type C Disease

Use of 2-Hydroxypropyl-Beta-Cyclodextrin for Niemann-Pick Type C Disease

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

Small molecules as therapeutic agents for inborn errors of metabolism

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