Substrate reduction therapy in four patients with milder CLN1 mutations and juvenile-onset batten disease using cysteamine bitartrate

M. Gavin, G. Y. Wen, J. Messing, S. Adelman, A. Logush, E. C. Jenkins, W. T. Brown, M. Velinov

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

21 Scopus citations

Abstract

Homozygous mutations in the gene CLN1 typically result in infantile-onset neuronal ceroid lipofuscinosis, a severe progressive neurological disorder with early death. The gene CLN1 encodes the enzyme palmitoyl protein thioesterase (PPT1), which is involved in lysosomal degradation of S-fatty acylated proteins. Cysteamine bitartrate (Cystagon) has been shown to reduce the storage material in PPT1 deficient cells. We report the results of a 7-year, open label, nonrandomized trial using Cystagon in four individuals with juvenile-onset NCL resulting from milder CLN1 mutations. The Cystagon doses were gradually increased with the goal of achieving 50 mg/kg bodyweight. The disease progression was monitored with parental questionnaires in four treated individuals and five untreated controls with the same CLN1 mutations. Mononuclear leukocytes from the treated individuals were examined for submicroscopic lysosomal storage inclusions. Cystagon treatment resulted in decreased storage material in peripheral leukocytes of the treated individuals. No severe side effects were noted. An allergic rash occurred in one of the individuals that required a dose reduction. The treatment did not result in overall attenuation of the disease progression. Slower progression of the disease was observed in two of the individuals when they were analyzed separately. However, slower progression in these individuals was also observed prior to starting the treatment. This effect may have been due to the higher Cystagon dose achieved in this group, but it could also have been coincidental. The apparent lack of toxicity of Cystagon may warrant further Cystagon trials in infantile NCL, possibly in conjunction with other developing therapies.

Original languageEnglish
Title of host publicationJIMD Reports
PublisherSpringer
Pages87-92
Number of pages6
DOIs
StatePublished - 2013
Externally publishedYes

Publication series

NameJIMD Reports
Volume11
ISSN (Print)2192-8304
ISSN (Electronic)2192-8312

Keywords

  • Batten disease
  • Disease severity score
  • Huntington disease
  • Neuronal ceroid lipofuscinoses
  • Observational group

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