This website aims to increase healthcare professional awareness of how Niemann-Pick type C (NP-C) might present and help you understand which symptoms. Niemann-Pick (NP) es una enfermedad lisosomal transmitida por herencia ( ). Enfermedad de Niemann-Pick tipo C. Revista Mexicana de Neurociencia . Keywords: Niemann-Pick (NP) disease, miglustat, clinical trial, treatment. Go to: .. Enfermedad de Niemann-Pick tipo C. Revista Mexicana de Neurociencia.
The aim of this systematic review was to analyse all the published clinical trials assessing treatments for Niemann-Pick NP disease. At present there are only trials investigating the treatment of NP disease type C. Furthermore, there is no uniformity among studies in treatment outcomes or in data analysis and presentation of results. As for cholesterol-lowering drugs, the combination of lovastatin, cholestyramine and nicotinic acid is the most effective one for lowering cholesterolemia.
Further research is much needed, and ongoing trials using enzyme replacement therapy might hopefully show promising results in the foreseeable future. Niemann-Pick NP disease is caused by an abnormality in lysosomes, which are unable to degrade macromolecules; as a result, the latter accumulate inside these organelles to form cellular inclusions 1 – 3.
NP disease encompasses a set of autosomal recessive hereditary abnormalities 1 characterized by the accumulation of lipids, mostly sphingomyelin and cholesterol, in different organs such as spleen or liver 145.
InBrady et al. Thus, the 4 disease types can be grouped into 2 main categories 14: Common manifestations of both disease types are hepatosplenomegaly and appearance of cherry-red spots in the retina 15 whereas neurodegeneration is only manifest in patients with NPA 4 NPC and NPD are characterized by a defect in the intracellular transport of low-density lipoprotein LDLwhich causes the accumulation of free un-esterified cholesterol and glycosphingolipids in multiple organs and tissues 410 – Although NPC symptoms are variable and can occur at any age 14when they start in early life the clinical presentation is characterized by more manifest, faster neuronal degeneration 1314 In general, the most common symptoms of NPC include hepatosplenomegaly and neurologic deterioration with ataxia, motor pathologies and horizontal saccadic eye movements HSEM 11141719 – Until some years ago, the treatment for NP disease was based on different drugs such as anti-epileptics, anticholinergic or antidepressants to alleviate symptoms, i.
In the NPA and NPB types, current research focuses on hematopoietic cell transplantation and enzyme replacement 5 At present, there is no cure for NP disease and potential therapies should be addressed. A main goal is to develop treatments in order to minimize both general symptoms and neurodegeneration. For this purpose, several clinical trials have been published to assess the effects, advantages and disadvantages of recently discovered treatments for NP disease.
Thus, the aim of this systematic review was to analyse all the clinical trials available in the literature assessing potential treatments for NP disease and to compare, when possible, the effectiveness of the different treatments.
A search was conducted in ScienceDirect and PubMed to identify all the clinical trials available for the treatment of NP disease. During the search, there were tkpo restrictions based on language or year of publication.
The data extracted from the clinical trials were: A total of 3, potential articles were identified, but only 15 of them were clinical trials performed in humans. Among them, 7 were excluded with reasons Figure 1. All of them focused on NPC. In most study cohorts the majority of se were women. Six of the clinical trials used miglustat Table 3. Treatment duration varied from 12 to 60 months and 2 studies 1329 allowed participants to continue with the intervention Table 3.
Outcome data on swallowing, language, manipulation, seizures, cognition, ocular movements and ambulation were limited, or not shown in two of the studies 1217 Table 4. Five of 6 trials divided their final results in subgroups depending on the disease course during the treatment Table 5.
In the study by Patterson et al. However, by observing the data shown in their published Figures, it can be inferred that: One of the participants in this trial did not have symptoms and his data were included as a control. The trial carried out by Wraith et al. Depending on the evolution of the participants in the different parameters, this trial determined the amount of patients who showed a stabilisation during treatment as follows: Using the abovementioned criteria, this study found that The trial of Heron et al.
Trial results were divided according to the onset of NP. The only patient with perinatal NP 2 months died during the trial. Among late childhood years patients, Finally, the trial by Fecarotta et al. However, during the treatment epistaxis and thrombocytopenia, insomnia, leukopenia, behavioural problems, extrapyramidal symptoms, tremors, itpo, and especially weight loss or diarrhea, were detected in some patients.
Of the selected clinical trials, all but one reported common disease symptoms at baseline, i. All of them reported the potential adverse effects of miglustat, i. The treatment effects on TC varied depending on the drug combinations and overall improved with the number of drugs: Although patients taking DMSO reported that they enfermeddad an unpleasant mouth odour, which in most cases remitted with chlorophyll, most adverse effects were associated with nicotinic acid: Other side effects such as hepatic enzyme changes, night-time agitation or constipation due to cholestyramine were also reported.
Unfortunately there is no uniformity among the different study outcomes, making it very pidk to conclude which is the most appropriate therapy that is currently available for NP. Miglustat was originally pjck for the treatment of GD and it was not until January that the European Union dnfermedad its use for the treatment of NPC 7. Miglustat inhibits glucosylceramide synthasethe enzyme responsible for catalysing the first step in the synthesis of most glycosphingolipids that accumulate in NPC 19thereby decreasing lysosomal storage This drug is able to cross the blood-brain barrier and delay the neurological manifestations in both adult and paediatric Enfermedas patients 13niemsnn In the scientific literature, clinical trials on NP are scarce, and some observational studies have reported on the effects of miglustat in NPC patients 2031 Preliminary findings by Galanaud and co-workers reported that miglustat had some beneficial effect on brain dysfunction oick NPC after a month treatment Findings of clinical trials are in agreement in that miglustat can slow the progression of neurological symptoms in all patients, yet the therapeutic benefit is greater in those with a late diagnosis i.
On enffrmedad other hand, there is no uniformity among published trials in the presentation of results. In addition, there are differences among studies in the neurological parameters reported. Furthermore, results within a study are not always shown for all trial groups, hampering potential comparisons between them.
Several adverse effects pici with miglustat such as diarrhea, flatulence, intestinal carbohydrate malabsorption pidk weight loss must be also underlined 12131724262934 Other forms of treatment are based on the use of cholesterol-lowering drugs or low cholesterol diets for the reduction of hepatic cholesterol.
The trial performed by Patterson and co-workers 28 was prior to the approval of miglustat as a therapy for NPC . Thus, the authors studied the effects of diet, DMSO for its effects on cholesterol transport and 3 drugs frequently used for the niwmann of hypercholesterolemia, i. The study showed important decreases in plasma and liver cholesterol levels, mainly due to the combination of lovastatin, cholestyramine and nicotinic acid.
Yet no information was reported on neurological progression. Unfortunately no treatment has yet proven able to change the actual course of NPC. Meanwhile, miglustat is the first and only specific drug approved for this disease in Europe , Canada  and Japan ; its objective is based on alleviating disease symptoms while attenuating neurodegeneration 13 The good news is that enzyme df therapy might represent a more promising treatment and there are currently two ongoing trials with recombinant human ASM for enfermrdad and elderly with NPB EudraCT reference numbers and In summary, at present there are only published clinical trials investigating the treatment for one specific type of NP disease, NPC.
Furthermore, there is no uniformity f study outcomes nor in the way the results were analysed and presented by the different authors.
Miglustat is expected to delay the neurological symptoms of NPC, with greater benefits in patients with a late onset of the disease. HPB-CD is also able to attenuate clinical symptoms engermedad it is not possible to compare the effectiveness of the two compounds owing to the limited data available for the latter.
Owing to the low number of clinical trials assessing NP treatment and niemznn lack of additional information, it is not yet possible to make a comparison between the different types of treatments for this disease. The authors have no conflicts of interest to declare. National Center for Biotechnology InformationU. Journal List Ann Transl Med v. Nuria Garatachea 1 4 5 Find articles by Nuria Garatachea.
Alejandro Lucia 1 7 Find articles by Alejandro Lucia. Author information Article notes Copyright and License information Disclaimer.
I Conception and design: All authors; II Administrative support: None; III Provision of study materials or patients: None; IV Collection and assembly of data: All authors; VI Manuscript writing: All authors; VII Final approval of manuscript: Received Oct 30; Accepted Nov Copyright Annals of Translational Medicine. This article has been cited by other articles in PMC. Abstract The aim of this systematic review was to analyse all tioo published clinical trials assessing treatments for Niemann-Pick NP disease.
Niemann-Pick NP disease, miglustat, clinical trial, treatment. Introduction Niemann-Pick NP disease is caused by an abnormality in lysosomes, which are unable to degrade macromolecules; as a result, the latter accumulate inside these organelles to form cellular inclusions 1 – 3. Methods Study selection A search was conducted in ScienceDirect and PubMed to identify all the clinical trials available for the treatment itpo NP enfdrmedad.
Open in a separate window. Table 1 Main characteristics of the clinical trials. Miglustat Six of the clinical trials used miglustat Table 3.
ENFERMEDAD DE NIEMANN-PICK: UN ENFOQUE GLOBAL. | Villamandos García | Revista ENE de Enfermería
Table 4 Results of clinical trials: Table 5 Results of clinical course proportion of patients showing improvement, no change or worsening of symptoms, and proportion of deaths. Other treatments Patterson et al. Footnotes Conflicts of Interest: Jan; 20 Suppl 1: Use of a protein sequence of enfermead and endolysosomal degradation.
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