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

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 - Orphanet J Rare Dis (2015)

Bottom Line: We compared the results after 24 months of treatment in 23 patients showing neurological manifestations.This conclusion applies particularly to patients with juvenile or adult onset of the disease.EudraCT number 2006-005842-35.

View Article: PubMed Central - PubMed

Affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. simona.fecarotta@gmail.com.

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.

Trial registration: EudraCT number 2006-005842-35.

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Related in: MedlinePlus

Evolution over time of the mean composite severity score (MCSS) during miglustat treatment in different groups of neurologically symptomatic patients, classified for the MCSS at baseline. Patients with a) MCSS ≤ 0.1 (n = 2), b) patients with MCSS between > 0.1 and ≤ 0.3 (n = 3), c) patients with MCSS > 0.3 and ≤ 0.5 (n = 7) and d) patients with MCSS > 0.5 (n = 11).
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Fig3: Evolution over time of the mean composite severity score (MCSS) during miglustat treatment in different groups of neurologically symptomatic patients, classified for the MCSS at baseline. Patients with a) MCSS ≤ 0.1 (n = 2), b) patients with MCSS between > 0.1 and ≤ 0.3 (n = 3), c) patients with MCSS > 0.3 and ≤ 0.5 (n = 7) and d) patients with MCSS > 0.5 (n = 11).

Mentions: The severity of clinical conditions at start of treatment was related to the progression rate. All patients with the most severe neurological involvement (MCSS > 0.5) did not show any improvement, while patients who were treated even with very mild neurological involvement were stable after 7 years of treatment. Progression of the disease was variable in patients with low and intermediate MCSS (Figure 3).Figure 3


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

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 - Orphanet J Rare Dis (2015)

Evolution over time of the mean composite severity score (MCSS) during miglustat treatment in different groups of neurologically symptomatic patients, classified for the MCSS at baseline. Patients with a) MCSS ≤ 0.1 (n = 2), b) patients with MCSS between > 0.1 and ≤ 0.3 (n = 3), c) patients with MCSS > 0.3 and ≤ 0.5 (n = 7) and d) patients with MCSS > 0.5 (n = 11).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359492&req=5

Fig3: Evolution over time of the mean composite severity score (MCSS) during miglustat treatment in different groups of neurologically symptomatic patients, classified for the MCSS at baseline. Patients with a) MCSS ≤ 0.1 (n = 2), b) patients with MCSS between > 0.1 and ≤ 0.3 (n = 3), c) patients with MCSS > 0.3 and ≤ 0.5 (n = 7) and d) patients with MCSS > 0.5 (n = 11).
Mentions: The severity of clinical conditions at start of treatment was related to the progression rate. All patients with the most severe neurological involvement (MCSS > 0.5) did not show any improvement, while patients who were treated even with very mild neurological involvement were stable after 7 years of treatment. Progression of the disease was variable in patients with low and intermediate MCSS (Figure 3).Figure 3

Bottom Line: We compared the results after 24 months of treatment in 23 patients showing neurological manifestations.This conclusion applies particularly to patients with juvenile or adult onset of the disease.EudraCT number 2006-005842-35.

View Article: PubMed Central - PubMed

Affiliation: Department of Translational Medicine-Section of Pediatrics, Federico II University, Naples, Italy. simona.fecarotta@gmail.com.

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.

Trial registration: EudraCT number 2006-005842-35.

Show MeSH
Related in: MedlinePlus