Investigative and emerging treatments for Batten disease

Abstract

Introduction: The neuronal ceroid lipofuscinoses (NCLs, or Batten disease) are a group of inherited neurodegenerative storage disorders that mostly affect children and young adults. Because no effective therapies are currently available, all prove fatal after a period of prolonged disability.

Areas covered: This review details the progress toward devising experimental therapies for the different forms of NCL. These approaches differ according to whether the gene defects are in soluble lysosomal enzymes or transmembrane proteins, but include enzyme replacement, gene therapy, neural stem cell approaches and small-molecule treatments. Not knowing the function of many of the gene products hampers the ability to produce a mechanistic-based therapy, especially in transmembrane-deficient forms of NCL.

Expert opinion: Promising progress has been made in preclinical studies for several forms of NCL, which has led to the initiation of clinical trials of several different experimental therapies. Nevertheless, challenges remain in how such preclinical advances can be translated successfully into a clinical setting. As new data about pathogenesis emerge it is likely that combination therapies that target different regions of the brain and/or body or different parts of the pathological cascade will be needed.

Keywords:

• Batten disease
• clinical trials
• combination treatments
• enzyme replacement
• gene therapy
• neural stem cell transplantation
• neuronal ceroid lipofuscinosis
• preclinical testing
• small-molecule therapies

Declaration of interest

MA Tarczyluk is working on a research project funded by BioMarin Pharmaceuticals, Inc. to characterizing a model of a different lysosomal storage disorder, so there is no conflict of interest. JD Cooper has in the past acted as a consultant for Stem Cell, Inc., which sponsored the clinical trials into the neural stem cell therapies for CLN1 disease and CLN2 disease. He also acts as a consultant for BioMarin, which sponsors a clinical trial of enzyme replacement therapy for CLN2 disease and continues to receive research funding from them. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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