Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label, controlled pilot study.
Mol Genet Metab
; 129(2): 80-90, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31839529
ABSTRACT
Central nervous system manifestations of mucopolysaccharidosis type I (MPS I) such as cognitive impairment, hydrocephalus, and spinal cord compression are inadequately treated by intravenously-administered enzyme replacement therapy with laronidase (recombinant human alpha-L-iduronidase). While hematopoietic stem cell transplantation treats neurological symptoms, this therapy is not generally offered to attenuated MPS I patients. This study is a randomized, open-label, controlled pilot study of intrathecal laronidase in eight attenuated MPS I patients with cognitive impairment. Subjects ranged between 12 years and 50 years old with a median age of 18 years. All subjects had received intravenous laronidase prior to the study over a range of 4 to 10 years, with a mean of 7.75 years. Weekly intravenous laronidase was continued throughout the duration of the study. The randomization period was one year, during which control subjects attended all study visits and assessments, but did not receive any intrathecal laronidase. After the first year, all eight subjects received treatment for one additional year. There was no significant difference in neuropsychological assessment scores between control or treatment groups, either over the one-year randomized period or at 18 or 24 months. However, there was no significant decline in scores in the control group either. Adverse events included pain (injection site, back, groin), headache, neck spasm, and transient blurry vision. There were seven serious adverse events, one judged as possibly related (headache requiring hospitalization). There was no significant effect of intrathecal laronidase on cognitive impairment in older, attenuated MPS I patients over a two-year treatment period. A five-year open-label extension study is underway.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Injeções Espinhais
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Mucopolissacaridose I
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Terapia de Reposição de Enzimas
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Disfunção Cognitiva
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Genet Metab
Assunto da revista:
BIOLOGIA MOLECULAR
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BIOQUIMICA
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METABOLISMO
Ano de publicação:
2020
Tipo de documento:
Article