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JIMD Reports, Volume 19 pp 11–22Cite as

Making the White Matter Matters: Progress in Understanding Canavan’s Disease and Therapeutic Interventions Through Eight Decades

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Part of the book series: JIMD Reports ((JIMD,volume 19))

Abstract

Canavan’s disease (CD) is a fatal autosomal recessive pediatric leukodystrophy in which patients show severe neurodegeneration and typically die by the age of 10, though life expectancy in patients can be highly variable. Currently, there is no effective treatment for CD; however, gene therapy seems to be a feasible approach to combat the disease. Being a monogenic defect, the disease provides an excellent model system to develop gene therapy approaches that can be extended to other monogenic leukodystrophies and neurodegenerative diseases. CD results from mutations in a single gene aspartoacylase which hydrolyses N-acetyl aspartic acid (NAA) which accumulates in its absences. Since CD is one of the few diseases that show high NAA levels, it can also be used to study the enigmatic biological role of NAA. The disease was first described in 1931, and this review traces the progress made in the past 8 decades to understand the disease by enumerating current hypotheses and ongoing palliative measures to alleviate patient symptoms in the context of the latest advances in the field.

Competing interests: None declared

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Acknowledgment

We would like to acknowledge the grant support from Jacob’s Cure, NTSAD Foundation, Canavan Foundation, and Public Health Service grants 1R01NS076991, P01 HL59407-11, P01 AI100263-01 from National Institutes of Health to GG.

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Authors and Affiliations

  1. University of Massachusetts Medical School, 368 Plantation Street, ASC6, Worcester, MA, 01605, USA

    Seemin S. Ahmed & Guangping Gao

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  1. Seemin S. Ahmed
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  2. Guangping Gao
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Correspondence to Guangping Gao .

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Editors and Affiliations

  1. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  2. Division for Metabolic Diseases, University Children´s Hospital, Zürich, Switzerland

    Matthias Baumgartner

  3. Tulane University Medical School, New Orleans, Louisiana, USA

    Eva Morava

  4. Division of Child and Adolescent Neurolo, Mayo Clinic, Rochester, USA

    Marc Patterson

  5. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom

    Shamima Rahman

  6. Centre for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Ivo Barić, M.D., PhD, Professor of Pediatrics

Appendices

One Sentence Synopsis

In this review, we follow the evolution of research on Canavan’s disease and discuss current understanding of molecular pathogenesis as well as developing potential therapeutics for the disease.

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Conflict of Interest

Seemin Seher Ahmed declares that she has no conflict of interest.

Guangping Gao is a founder of Voyager Therapeutics and holds equity in the company. He is also an inventor on patents with potential royalties licensed to Voyager Therapeutics. Voyager Therapeutics is a newly launched gene therapy company that focuses on using the recombinant adeno-associated virus platform technology for the development of gene therapeutics to treat a wide range of CNS disorders.

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This article directly does not contain any studies with human subjects performed by the authors.

Animal Rights

All institutional and national guidelines for the care and use of laboratory animals were followed in the work done in the authors’ laboratory.

Details of the Contributions of Individual Authors

Seemin Seher Ahmed planned and drafted the review.

Guangping Gao reviewed the drafts and provided critical inputs.

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Ahmed, S.S., Gao, G. (2014). Making the White Matter Matters: Progress in Understanding Canavan’s Disease and Therapeutic Interventions Through Eight Decades. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 19. JIMD Reports, vol 19. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_356

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