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Brief Report
September 8, 2020

Association of Miglustat With Swallowing Outcomes in Niemann-Pick Disease, Type C1

Author Affiliations
  • 1Speech-Language Pathology Section, Rehabilitation Medicine Department, Mark O. Hatfield Clinical Center, Bethesda, Maryland
  • 2Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
  • 3Biostatistics and Clinical Epidemiology Service, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland
JAMA Neurol. Published online September 8, 2020. doi:10.1001/jamaneurol.2020.3241
Key Points

Question  Does miglustat use preserve swallowing function in individuals with Niemann-Pick disease, type C1?

Findings  In this cohort study of 50 individuals with Niemann-Pick disease, type C1 with neurologic disease onset before age 15 years, miglustat use was associated with stabilized swallowing function and reduced aspiration risk. Untreated patients were more likely to progress in swallowing dysfunction and have worse aspiration risk than those receiving miglustat therapy.

Meaning  This finding supports the efficacy of miglustat therapy in Niemann-Pick disease, type C1 in reducing aspiration risk and improving quality of life due to progressive oropharyngeal swallowing dysfunction aspiration pneumonia.


Importance  Niemann-Pick disease, type C1 (NPC1) is a progressive neurovisceral disease with no US Food and Drug Administration–approved therapy. Miglustat, a drug used off-label in the United States for the treatment of NPC1, appears to stabilize neurologic disease progression. Several prospective trials suggest that miglustat stabilizes oropharyngeal swallowing function; however, its effect on dysphagia and aspiration risk has not been demonstrated instrumentally.

Objective  To determine if miglustat therapy is associated with stabilized swallowing dysfunction in individuals with NPC1.

Design, Setting, and Participants  Patients with confirmed NPC1 diagnoses were evaluated in a single-center cohort study of NPC1 from April 1997 to November 2019. Longitudinal data from individuals with neurologic disease onset prior to age 15 years were analyzed. The study population was divided into those with neurologic disease onset in early childhood (age <6 years) and late childhood (age ≥6 years and <15 years). Analysis began September 2019.

Exposures  Oral miglustat at baseline and at follow-up.

Main Outcomes and Measures  Oropharyngeal swallowing function was assessed with videofluoroscopic swallowing studies. Overall swallowing ability and aspiration risk were evaluated using the American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain and an adapted Rosenbek aspiration-penetration scale, respectively.

Results  Overall, 50 participants were evaluated at baseline (median [interquartile range] age, 9.4 [3.4-16.4] years; 26 [52%] female). The median (interquartile range) duration of follow-up was 3.0 (1.1-4.4) years. Miglustat use was associated with decreased odds of worse American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain outcomes in all 3 subsets (overall: odds ratio [OR], 0.09 [95% CI, 0.02-0.36); P < .001; early childhood: OR, 0.17 [95% CI, 0.04-0.67]; P = .01; late childhood: OR, 0.05 [95% CI, 0.01-0.29]; P = .001). Miglustat use was associated with decreased odds of worse Rosenbek aspiration-penetration scale outcomes in the overall cohort (OR, 0.28 [95% CI, 0.08-0.95]; P = .04) but not in each subgroup (early childhood: OR, 0.27 [95% CI, 0.06-1.22]; P = .09; late childhood: OR, 0.38 [95% CI, 0.06-2.33]; P = .29).

Conclusions and Relevance  These data suggest that miglustat use is associated with stabilized swallowing function and reduced aspiration risk in NPC1, thus supporting its use in this population. In addition, these data demonstrate that a quantification of swallowing dysfunction can be used as a clinically relevant, functional outcome measure in future therapeutic trials in NPC1.

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