Type C Niemann-Pick Disease (Niemann Pick Disease, Type C)

An autosomal recessive lipid storage disorder that is characterized by accumulation of CHOLESTEROL and SPHINGOMYELINS in cells of the VISCERA and the CENTRAL NERVOUS SYSTEM. Type C (or C1) and type D are allelic disorders caused by mutation of the NPC1 gene, which encodes a protein that mediates intracellular cholesterol transport from LYSOSOMES. Clinical signs include hepatosplenomegaly and chronic neurological symptoms. Type D is a variant in people with a Nova Scotia ancestry.

Also Known As:

Niemann Pick Disease, Type C; Niemann Pick Disease, Type D; Niemann-Pick Disease, Type C; Neurovisceral Storage Disease with Vertical Supranuclear Ophthalmoplegia; Niemann-Pick Disease Type D; Niemann-Pick Disease with Cholesterol Esterification Block; Niemann-Pick Disease without Sphingomyelinase Deficiency; Niemann-Pick Disease, Chronic Neuronopathic Form; Niemann-Pick Disease, Nova Scotian; Niemann-Pick Disease, Type C1; Niemann-Pick disease, Subacute Juvenile Form; Niemann-Pick's Disease Type C; Niemann-Pick's Disease Type D; Nova Scotia (Type D) Form of Niemann-Pick Disease; Nova Scotia Niemann-Pick Disease (Type D); Niemann Pick Disease Type C; Niemann Pick Disease Type D; Niemann Pick Disease with Cholesterol Esterification Block; Niemann Pick Disease without Sphingomyelinase Deficiency; Niemann Pick Disease, Chronic Neuronopathic Form; Niemann Pick Disease, Nova Scotian; Niemann Pick Disease, Type C1; Niemann Pick Type C Disease; Niemann Pick Type D Disease; Niemann Pick disease, Subacute Juvenile Form; Niemann Pick's Disease Type C; Niemann Pick's Disease Type D; Nova Scotia Niemann Pick Disease (Type D); Niemann-Pick Disease Type C; Niemann-Pick Disease, Type D; Niemann-Pick Type C Disease; Niemann-Pick Type D Disease

Networked: 826 relevant articles (30 outcomes, 54 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Neurologic Manifestations (Neurological Manifestations)
2.	Neurodegenerative Diseases (Neurodegenerative Disease)
3.	Ataxia (Dyssynergia)
4.	Seizures (Absence Seizure)
5.	Disease Progression

Experts

1.	Porter, Forbes D: 37 articles (01/2022 - 10/2010)
2.	Platt, Frances M: 27 articles (01/2022 - 08/2004)
3.	Vanier, Marie T: 25 articles (01/2020 - 07/2002)
4.	Ory, Daniel S: 20 articles (10/2021 - 03/2008)
5.	Irie, Tetsumi: 19 articles (01/2022 - 01/2013)
6.	Ohno, Kousaku: 19 articles (01/2021 - 09/2002)
7.	Patterson, Marc C: 18 articles (11/2021 - 10/2003)
8.	Higaki, Katsumi: 14 articles (04/2022 - 06/2004)
9.	Higashi, Taishi: 14 articles (01/2022 - 01/2014)
10.	Ishitsuka, Yoichi: 14 articles (01/2022 - 01/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Type C Niemann-Pick Disease:

1.	miglustat (Zavesca)FDA Link 02/27/2015 - "Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C." 01/01/2013 - "Long-term efficacy of miglustat in paediatric patients with Niemann-Pick disease type C." 12/01/2020 - "Association of Miglustat With Swallowing Outcomes in Niemann-Pick Disease, Type C1." 01/01/2020 - "Miglustat has been indicated for the treatment of Niemann-Pick disease type C (NP-C) since 2009. " 01/01/2020 - "Long-term survival outcomes of patients with Niemann-Pick disease type C receiving miglustat treatment: A large retrospective observational study."
2.	CholesterolIBA 08/20/2010 - "Exosome secretion ameliorates lysosomal storage of cholesterol in Niemann-Pick type C disease." 11/01/1998 - "Reduced cholesterol accumulation and improved deficient peroxisomal functions in a murine model of Niemann-Pick type C disease upon treatment with peroxisomal proliferators." 12/01/2022 - "Intravenous 2-hydroxypropyl-β-cyclodextrin (Trappsol® Cyclo™) demonstrates biological activity and impacts cholesterol metabolism in the central nervous system and peripheral tissues in adult subjects with Niemann-Pick Disease Type C1: Results of a phase 1 trial." 08/03/2017 - "The drug 2-hydroxypropyl-β-cyclodextrin (HPβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease, type C (NPC) and has been advanced to human clinical trials. " 10/21/2014 - "Niemann-Pick type C disease: a QM/MM study of conformational changes in cholesterol in the NPC1(NTD) and NPC2 binding pockets."
3.	acetylleucineIBA 03/01/2022 - "To investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann-Pick disease type C (NPC) patients. " 03/01/2022 - "Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C." 01/01/2022 - "In an open-label study, N-acetyl-l-leucine administered for 6-weeks significantly improved clinical impression of change, ataxia, and quality of life in patients with Niemann-Pick disease type C1. " 01/01/2021 - "In observational clinical studies, acetyl-dl-leucine improved symptoms of ataxia, in particular in patients with the lysosomal storage disorder, Niemann-Pick disease type C1. " 01/01/2021 - "In agreement with these pre-clinical data, when Niemann-Pick disease type C1 patients were evaluated after 12 months of acetyl-dl-leucine treatment, rates of disease progression were slowed, with stabilization or improvement in multiple neurological domains. "
4.	2-Hydroxypropyl-beta-cyclodextrinIBA 02/01/2019 - "2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is used in the formulation of drugs and recently orphan designation was granted for the treatment of Niemann-Pick disease, type C. " 01/01/2019 - "2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is utilized in the formulation of pharmaceutical products and recently orphan designation was granted for the treatment of Niemann-Pick disease, type C. " 09/01/2018 - "A new methodology, based on high resolution liquid chromatography with light scatterin detector, is applied to analyze Hydroxypropyl-beta-Cyclodextrin (HPβCD) in urine samples of a child affected by Niemann-Pick Type C disease. " 05/01/2017 - "Early experience with compassionate use of 2 hydroxypropyl-beta-cyclodextrin for Niemann-Pick type C disease: review of initial published cases." 01/01/2017 - "2-Hydroxypropyl-beta-cyclodextrin (HPβCD) has gained recent attention as a potential therapeutic intervention in the treatment of the rare autosomal-recessive, neurodegenerative lysosomal storage disorder Niemann-Pick Disease Type C1 (NPC1). "
5.	Dimethyl Sulfoxide (DMSO)FDA LinkGeneric 08/01/1988 - "Clinical improvement with DMSO treatment in a patient with Niemann-Pick disease (type C)." 12/01/1995 - "We treated patients with Niemann-Pick disease type C by oral administration of DMSO, resulting in some clinical benefits such as decreased size of hepatosplenomegaly, and lesser frequency of seizures with improved EEG. " 11/28/1989 - "Type C Niemann-Pick disease: dimethyl sulfoxide moderates abnormal LDL-cholesterol processing in mutant fibroblasts." 09/02/1988 - "Treatment with 2% DMSO caused a marked increase in sphingomyelinase activities at pH 5.0 and 7.5 in normal and Niemann-Pick disease type C cells, while in type A and B cells, both activities remained virtually unchanged after DMSO treatment. "
6.	Valproic Acid (Depakote)FDA LinkGeneric 01/01/2017 - "Encouragingly, several compounds such as valproic acid and X5050 that target REST/NRSF have been shown to be clinically effective at rescuing seizures or Niemann-Pick type C disease. " 08/31/2007 - "Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann-Pick type C disease improved by valproic acid, a histone deacetylase inhibitor."
7.	Proteins (Proteins, Gene)FDA Link 01/01/2023 - "Identification and characterization of protein interactions with the major Niemann-Pick type C disease protein in yeast reveals pathways of therapeutic potential." 01/01/2023 - "Niemann-Pick disease type C1 (NP-C) is a prematurely lethal genetic lysosomal storage disorder with neurological and visceral pathology resulting from mutations in the NPC1 gene encoding the lysosomal transmembrane protein NPC1. " 01/01/2019 - "Functional analysis of Niemann-Pick disease type C family protein, NPC1a, in Drosophila melanogaster." 01/01/2018 - "Primary cilium alterations and expression changes of Patched1 proteins in niemann-pick type C disease." 01/01/2017 - "Phenanthridin-6-one derivatives as the first class of non-steroidal pharmacological chaperones for Niemann-Pick disease type C1 protein."
8.	Biomarkers (Surrogate Marker)IBA 01/01/2023 - "Neurofilament light chain in cerebrospinal fluid as a novel biomarker in evaluating both clinical severity and therapeutic response in Niemann-Pick disease type C1." 12/01/2022 - "In Niemann-Pick type C disease, such a panel performed better than individual biomarkers. " 12/01/2022 - "Using Niemann-Pick type C disease (NPC) as a paradigm, we aimed to improve biomarker discovery in patients with neurometabolic disorders. " 12/01/2022 - "Niemann-Pick type C disease as proof-of-concept for intelligent biomarker panel selection in neurometabolic disorders." 01/01/2022 - "Searching, Structural Determination, and Diagnostic Performance Evaluation of Biomarker Molecules for Niemann-Pick Disease Type C Using Liquid Chromatography/Tandem Mass Spectrometry."
9.	arimoclomolIBA 11/01/2021 - "Efficacy and safety of arimoclomol in Niemann-Pick disease type C: Results from a double-blind, randomised, placebo-controlled, multinational phase 2/3 trial of a novel treatment." 01/01/2016 - "Oral administration of arimoclomol, a small-molecule coinducer of HSPs that is currently in clinical trials for Niemann-Pick disease type C (NPC), recapitulated the effects of recombinant human HSP70, suggesting that heat shock protein-based therapies merit clinical evaluation for treating LSDs."
10.	CyclodextrinsIBA 12/01/2023 - "Hydroxypropyl-β-cyclodextrin (HP-β-CD) has been used as a therapeutic agent for Niemann-Pick disease Type C (NPC). " 11/01/2020 - "Investigating the Mechanism of Cyclodextrins in the Treatment of Niemann-Pick Disease Type C Using Crosslinked 2-Hydroxypropyl-β-cyclodextrin." 10/21/2019 - "Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis." 01/01/2019 - "Over the last decade, cyclodextrins (CDs) have gained considerable attention as a potential therapeutic intervention in the treatment of the rare genetic condition Niemann-Pick type C disease (NPC). " 09/01/2018 - "Application of a simple methodology to analyze Hydroxypropyl-β-Cyclodextrin in urine using HPLC-LS in early Niemann-Pick disease type C patient."

Therapies and Procedures

1.	Therapeutics 01/18/2023 - "β-CDs have also shown promise as therapeutics for treatment of some lysosomal storage disorders, such as Niemann-Pick disease type C, and other disease states which involve metabolite accumulation in the lysosome. " 06/01/2021 - "Successful implementation of classical ketogenic dietary therapy in a patient with Niemann-Pick disease type C." 01/01/2021 - "Niemann-Pick Disease, Type C: Diagnosis, Management and Disease-Targeted Therapies in Development." 12/01/2020 - "Niemann-Pick disease, type C1 (NPC1) is a progressive neurovisceral disease with no US Food and Drug Administration-approved therapy. " 01/01/2019 - "Niemann-Pick disease type C (NPC) is a fatal neurodegenerative condition with no FDA-approved therapy. "
2.	Diet Therapy (Therapy, Diet) 09/01/2015 - "Seventy-five trials (44.4%) reported potential efficacy, of which only 2 therapies are now established treatments, namely, dietary restriction for phenylketonuria and miglustat for Niemann-Pick disease type C. " 09/01/2022 - "The major metabolic and genetic treatable ataxic disorders include ataxia with vitamin E deficiency, abetalipoproteinemia, cerebrotendinous xanthomatosis, Niemann-Pick disease type C, autosomal recessive cerebellar ataxia due to coenzyme Q10 deficiency, glucose transporter type 1 deficiency, and episodic ataxia type 2. The treatment of these disorders includes the replacement of deficient cofactors and vitamins, dietary modifications, and other specific treatments. "
3.	Oral Administration 12/01/1995 - "We treated patients with Niemann-Pick disease type C by oral administration of DMSO, resulting in some clinical benefits such as decreased size of hepatosplenomegaly, and lesser frequency of seizures with improved EEG. " 01/01/2016 - "Oral administration of arimoclomol, a small-molecule coinducer of HSPs that is currently in clinical trials for Niemann-Pick disease type C (NPC), recapitulated the effects of recombinant human HSP70, suggesting that heat shock protein-based therapies merit clinical evaluation for treating LSDs."
4.	Investigational Therapies (Experimental Therapy) 07/01/2010 - "2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) is a promising experimental therapy for Niemann-Pick type C disease that improved intracellular cholesterol transport, substantially reduced neurodegeneration and hepatic disease, and increased lifespan in npc1 mice. " 01/01/2020 - "2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) is an experimental therapy for Niemann-Pick disease type C (NPC) that reduced neuronal cholesterol and ganglioside storage, reduced Purkinje cell death, and increased lifespan in npc1-/- mice and NPC1 cats. " 09/01/2017 - "Here, we review the current evidence for mitochondrial dysfunction in neuronal models of seven LSD, including GM1-gangliosidosis, mucopolysaccharidosis IIIC, multiple sulfatase deficiency, Krabbe disease, Gaucher disease, Niemann Pick disease type C and the neural ceroid lipofuscinoses and outline current experimental therapies aimed at restoring mitochondrial function and neuroprotection in LSD."
5.	Palliative Care (Palliative Therapy) 06/01/2021 - "Niemann-Pick disease type C (NP-C) is a neurodegenerative disease for which only palliative treatment exists, and only miglustat is effective in stabilizing neurological manifestations of NP-C. "