Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C

Simona Fecarotta, Alfonso Romano, Roberto Della Casa, Ennio Del Giudice, Diana Bruschini, Giuseppina Mansi, Bruno Bembi, Andrea Dardis, Agata Fiumara, Maja Di Rocco, Graziella Uziel, Anna Ardissone, Dario Roccatello, Mirella Alpa, Enrico Bertini, Adele D'Amico, Carlo Dionisi-Vici, Federica Deodato, Stefania Caviglia, Antonio FedericoSilvia Palmeri, Orazio Gabrielli, Lucia Santoro, Alessandro Filla, Cinzia Russo, Giancarlo Parenti, Generoso Andria

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Twenty-five patients with Niemann Pick disease type C (age range: 7 months to 44 years) were enrolled in an Italian independent multicenter trial and treated with miglustat for periods from 48 to 96 months. Methods: Based on the age at onset of neurological manifestations patients' phenotypes were classified as: adult (n = 6), juvenile (n = 9), late infantile (n = 6), early infantile (n = 2). Two patients had an exclusively visceral phenotype. We clinically evaluated patients' neurological involvement, giving a score of severity ranging from 0 (best) to 3 (worst) for gait abnormalities, dystonia, dysmetria, dysarthria, and developmental delay/cognitive impairment, and from 0 to 4 for dysphagia. We calculated a mean composite severity score transforming the original scores proportionally to range from 0 to 1 to summarize the clinical picture of patients and monitor their clinical course. Results: We compared the results after 24 months of treatment in 23 patients showing neurological manifestations. Stabilization or improvement of all parameters was observed in the majority of patients. With the exception of developmental delay/cognitive impairment, these results persisted after 48-96 months in 41 - 55% of the patients (dystonia: 55%, dysarthria: 50%, gait abnormalities: 43%, dysmetria: 41%, respectively). After 24 months of therapy the majority of the evaluable patients (n = 20), demonstrated a stabilization or improvement in the ability to swallow four substances of different consistency (water: 65%, purée: 58%, little pasta: 60%, biscuit: 55%). These results persisted after 48-96 months in 40-50% of patients, with the exception of water swallowing. Stabilization or improvement of the composite severity score was detected in the majority (57%) of 7 patients who were treated early (within 3.5 years from onset) and rarely in patients who received treatment later. Conclusions: The results of this study suggest that miglustat treatment can improve or stabilize neurological manifestations, at least for a period of time; the severity of clinical conditions at the beginning of treatment can influence the rate of disease progression. This conclusion applies particularly to patients with juvenile or adult onset of the disease.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalOrphanet Journal of Rare Diseases
DOIs
Publication statusAccepted/In press - Feb 27 2015

Fingerprint

Type C Niemann-Pick Disease
Neurologic Manifestations
Dysarthria
Cerebellar Ataxia
Dystonia
Deglutition
Gait
miglustat
Phenotype
Therapeutics
Aptitude
Water
Deglutition Disorders
Age of Onset

Keywords

  • Miglustat
  • NB-DNJ
  • Niemann-Pick disease type C
  • NPC
  • Substrate reduction therapy
  • Therapy
  • Treatment

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Fecarotta, S., Romano, A., Della Casa, R., Del Giudice, E., Bruschini, D., Mansi, G., ... Andria, G. (Accepted/In press). Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C. Orphanet Journal of Rare Diseases, 1-11. https://doi.org/10.1186/s13023-015-0240-y

Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C. / Fecarotta, Simona; Romano, Alfonso; Della Casa, Roberto; Del Giudice, Ennio; Bruschini, Diana; Mansi, Giuseppina; Bembi, Bruno; Dardis, Andrea; Fiumara, Agata; Di Rocco, Maja; Uziel, Graziella; Ardissone, Anna; Roccatello, Dario; Alpa, Mirella; Bertini, Enrico; D'Amico, Adele; Dionisi-Vici, Carlo; Deodato, Federica; Caviglia, Stefania; Federico, Antonio; Palmeri, Silvia; Gabrielli, Orazio; Santoro, Lucia; Filla, Alessandro; Russo, Cinzia; Parenti, Giancarlo; Andria, Generoso.

In: Orphanet Journal of Rare Diseases, 27.02.2015, p. 1-11.

Research output: Contribution to journalArticle

Fecarotta, S, Romano, A, Della Casa, R, Del Giudice, E, Bruschini, D, Mansi, G, Bembi, B, Dardis, A, Fiumara, A, Di Rocco, M, Uziel, G, Ardissone, A, Roccatello, D, Alpa, M, Bertini, E, D'Amico, A, Dionisi-Vici, C, Deodato, F, Caviglia, S, Federico, A, Palmeri, S, Gabrielli, O, Santoro, L, Filla, A, Russo, C, Parenti, G & Andria, G 2015, 'Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C', Orphanet Journal of Rare Diseases, pp. 1-11. https://doi.org/10.1186/s13023-015-0240-y
Fecarotta, Simona ; Romano, Alfonso ; Della Casa, Roberto ; Del Giudice, Ennio ; Bruschini, Diana ; Mansi, Giuseppina ; Bembi, Bruno ; Dardis, Andrea ; Fiumara, Agata ; Di Rocco, Maja ; Uziel, Graziella ; Ardissone, Anna ; Roccatello, Dario ; Alpa, Mirella ; Bertini, Enrico ; D'Amico, Adele ; Dionisi-Vici, Carlo ; Deodato, Federica ; Caviglia, Stefania ; Federico, Antonio ; Palmeri, Silvia ; Gabrielli, Orazio ; Santoro, Lucia ; Filla, Alessandro ; Russo, Cinzia ; Parenti, Giancarlo ; Andria, Generoso. / Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C. In: Orphanet Journal of Rare Diseases. 2015 ; pp. 1-11.
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abstract = "Background: Twenty-five patients with Niemann Pick disease type C (age range: 7 months to 44 years) were enrolled in an Italian independent multicenter trial and treated with miglustat for periods from 48 to 96 months. Methods: Based on the age at onset of neurological manifestations patients' phenotypes were classified as: adult (n = 6), juvenile (n = 9), late infantile (n = 6), early infantile (n = 2). Two patients had an exclusively visceral phenotype. We clinically evaluated patients' neurological involvement, giving a score of severity ranging from 0 (best) to 3 (worst) for gait abnormalities, dystonia, dysmetria, dysarthria, and developmental delay/cognitive impairment, and from 0 to 4 for dysphagia. We calculated a mean composite severity score transforming the original scores proportionally to range from 0 to 1 to summarize the clinical picture of patients and monitor their clinical course. Results: We compared the results after 24 months of treatment in 23 patients showing neurological manifestations. Stabilization or improvement of all parameters was observed in the majority of patients. With the exception of developmental delay/cognitive impairment, these results persisted after 48-96 months in 41 - 55{\%} of the patients (dystonia: 55{\%}, dysarthria: 50{\%}, gait abnormalities: 43{\%}, dysmetria: 41{\%}, respectively). After 24 months of therapy the majority of the evaluable patients (n = 20), demonstrated a stabilization or improvement in the ability to swallow four substances of different consistency (water: 65{\%}, pur{\'e}e: 58{\%}, little pasta: 60{\%}, biscuit: 55{\%}). These results persisted after 48-96 months in 40-50{\%} of patients, with the exception of water swallowing. Stabilization or improvement of the composite severity score was detected in the majority (57{\%}) of 7 patients who were treated early (within 3.5 years from onset) and rarely in patients who received treatment later. Conclusions: The results of this study suggest that miglustat treatment can improve or stabilize neurological manifestations, at least for a period of time; the severity of clinical conditions at the beginning of treatment can influence the rate of disease progression. This conclusion applies particularly to patients with juvenile or adult onset of the disease.",
keywords = "Miglustat, NB-DNJ, Niemann-Pick disease type C, NPC, Substrate reduction therapy, Therapy, Treatment",
author = "Simona Fecarotta and Alfonso Romano and {Della Casa}, Roberto and {Del Giudice}, Ennio and Diana Bruschini and Giuseppina Mansi and Bruno Bembi and Andrea Dardis and Agata Fiumara and {Di Rocco}, Maja and Graziella Uziel and Anna Ardissone and Dario Roccatello and Mirella Alpa and Enrico Bertini and Adele D'Amico and Carlo Dionisi-Vici and Federica Deodato and Stefania Caviglia and Antonio Federico and Silvia Palmeri and Orazio Gabrielli and Lucia Santoro and Alessandro Filla and Cinzia Russo and Giancarlo Parenti and Generoso Andria",
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T1 - Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C

AU - Fecarotta, Simona

AU - Romano, Alfonso

AU - Della Casa, Roberto

AU - Del Giudice, Ennio

AU - Bruschini, Diana

AU - Mansi, Giuseppina

AU - Bembi, Bruno

AU - Dardis, Andrea

AU - Fiumara, Agata

AU - Di Rocco, Maja

AU - Uziel, Graziella

AU - Ardissone, Anna

AU - Roccatello, Dario

AU - Alpa, Mirella

AU - Bertini, Enrico

AU - D'Amico, Adele

AU - Dionisi-Vici, Carlo

AU - Deodato, Federica

AU - Caviglia, Stefania

AU - Federico, Antonio

AU - Palmeri, Silvia

AU - Gabrielli, Orazio

AU - Santoro, Lucia

AU - Filla, Alessandro

AU - Russo, Cinzia

AU - Parenti, Giancarlo

AU - Andria, Generoso

PY - 2015/2/27

Y1 - 2015/2/27

N2 - Background: Twenty-five patients with Niemann Pick disease type C (age range: 7 months to 44 years) were enrolled in an Italian independent multicenter trial and treated with miglustat for periods from 48 to 96 months. Methods: Based on the age at onset of neurological manifestations patients' phenotypes were classified as: adult (n = 6), juvenile (n = 9), late infantile (n = 6), early infantile (n = 2). Two patients had an exclusively visceral phenotype. We clinically evaluated patients' neurological involvement, giving a score of severity ranging from 0 (best) to 3 (worst) for gait abnormalities, dystonia, dysmetria, dysarthria, and developmental delay/cognitive impairment, and from 0 to 4 for dysphagia. We calculated a mean composite severity score transforming the original scores proportionally to range from 0 to 1 to summarize the clinical picture of patients and monitor their clinical course. Results: We compared the results after 24 months of treatment in 23 patients showing neurological manifestations. Stabilization or improvement of all parameters was observed in the majority of patients. With the exception of developmental delay/cognitive impairment, these results persisted after 48-96 months in 41 - 55% of the patients (dystonia: 55%, dysarthria: 50%, gait abnormalities: 43%, dysmetria: 41%, respectively). After 24 months of therapy the majority of the evaluable patients (n = 20), demonstrated a stabilization or improvement in the ability to swallow four substances of different consistency (water: 65%, purée: 58%, little pasta: 60%, biscuit: 55%). These results persisted after 48-96 months in 40-50% of patients, with the exception of water swallowing. Stabilization or improvement of the composite severity score was detected in the majority (57%) of 7 patients who were treated early (within 3.5 years from onset) and rarely in patients who received treatment later. Conclusions: The results of this study suggest that miglustat treatment can improve or stabilize neurological manifestations, at least for a period of time; the severity of clinical conditions at the beginning of treatment can influence the rate of disease progression. This conclusion applies particularly to patients with juvenile or adult onset of the disease.

AB - Background: Twenty-five patients with Niemann Pick disease type C (age range: 7 months to 44 years) were enrolled in an Italian independent multicenter trial and treated with miglustat for periods from 48 to 96 months. Methods: Based on the age at onset of neurological manifestations patients' phenotypes were classified as: adult (n = 6), juvenile (n = 9), late infantile (n = 6), early infantile (n = 2). Two patients had an exclusively visceral phenotype. We clinically evaluated patients' neurological involvement, giving a score of severity ranging from 0 (best) to 3 (worst) for gait abnormalities, dystonia, dysmetria, dysarthria, and developmental delay/cognitive impairment, and from 0 to 4 for dysphagia. We calculated a mean composite severity score transforming the original scores proportionally to range from 0 to 1 to summarize the clinical picture of patients and monitor their clinical course. Results: We compared the results after 24 months of treatment in 23 patients showing neurological manifestations. Stabilization or improvement of all parameters was observed in the majority of patients. With the exception of developmental delay/cognitive impairment, these results persisted after 48-96 months in 41 - 55% of the patients (dystonia: 55%, dysarthria: 50%, gait abnormalities: 43%, dysmetria: 41%, respectively). After 24 months of therapy the majority of the evaluable patients (n = 20), demonstrated a stabilization or improvement in the ability to swallow four substances of different consistency (water: 65%, purée: 58%, little pasta: 60%, biscuit: 55%). These results persisted after 48-96 months in 40-50% of patients, with the exception of water swallowing. Stabilization or improvement of the composite severity score was detected in the majority (57%) of 7 patients who were treated early (within 3.5 years from onset) and rarely in patients who received treatment later. Conclusions: The results of this study suggest that miglustat treatment can improve or stabilize neurological manifestations, at least for a period of time; the severity of clinical conditions at the beginning of treatment can influence the rate of disease progression. This conclusion applies particularly to patients with juvenile or adult onset of the disease.

KW - Miglustat

KW - NB-DNJ

KW - Niemann-Pick disease type C

KW - NPC

KW - Substrate reduction therapy

KW - Therapy

KW - Treatment

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