Advances in the treatment of neuronal ceroid lipofuscinosis

Jonathan B. Rosenberg, Alvin Chen, Stephen M. Kaminsky, Ronald G. Crystal, Dolan Sondhi

Research output: Contribution to journalReview article


Introduction: Neuronal ceroid lipofuscinoses (NCL) are neurodegenerative lysosomal storage disorders typically characterized by cognitive and visual impairments, epileptic seizures, ataxia, and deterioration of motor skills. Recent success of Brineura® for the treatment of neurologic manifestations of CLN2 disease has led to renewed interest in therapeutics for NCL. Despite complex challenges associated with CNS therapy, treatment modalities such as enzyme replacement therapy, gene therapy, stem cell therapy, and small molecule pharmacotherapy have been evaluated. Owing to the complexity of clinical endpoints which are often reliant on subjective clinical scales for the evaluation of candidate therapies, development of quantitative biomarkers for NCLs has become a necessity for the validation of potential treatments. Areas covered: For each NCL subtype, this review covers natural histories, animal models, biomarkers, therapeutic approaches, and preclinical and clinical research for therapeutic development. It corresponds to literature covering the years 1968-2019, with emphasis on the last decade. Expert opinion: Much progress has been made in NCL research, including better animal models, biomarkers and improved therapeutics with many of them reaching the clinical trial stage. In the future, successful therapies may involve the combination of two or more therapeutic modalities to provide therapeutic benefit especially as the patients grow older.

Original languageEnglish
Pages (from-to)473-500
Number of pages28
JournalExpert Opinion on Orphan Drugs
Issue number11
Publication statusPublished - 2 Nov 2019



  • adeno-associated virus (AAV)
  • ceroid lipofuscinosis
  • clinical trials
  • enzyme replacement therapy (ERT)
  • gene therapy
  • neuronal (CLN)
  • Neuronal ceroid lipofuscinoses (NCL)
  • palmitoyl protein thioesterase-1 (PPT1)
  • tripeptidyl peptidase-1 (TPP1)

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
  • Health Policy
  • Pharmacology (medical)

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