Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jan;81(1):101-123.
doi: 10.1007/s40265-020-01440-7.

Neuronal Ceroid Lipofuscinosis: Potential for Targeted Therapy

Nicola Specchio  1 , Alessandro Ferretti  2 , Marina Trivisano  2 , Nicola Pietrafusa  2 , Chiara Pepi  2   3 , Costanza Calabrese  2 , Susanna Livadiotti  4 , Alessandra Simonetti  4 , Paolo Rossi  5   6 , Paolo Curatolo  3 , Federico Vigevano  7
Affiliations
Review

Neuronal Ceroid Lipofuscinosis: Potential for Targeted Therapy

Nicola Specchio et al. Drugs. 2021 Jan.

Abstract

Neuronal ceroid lipofuscinosis (NCLs) is a group of inherited neurodegenerative lysosomal storage diseases that together represent the most common cause of dementia in children. Phenotypically, patients have visual impairment, cognitive and motor decline, epilepsy, and premature death. A primary challenge is to halt and/or reverse these diseases, towards which developments in potential effective therapies are encouraging. Many treatments, including enzyme replacement therapy (for CLN1 and CLN2 diseases), stem-cell therapy (for CLN1, CLN2, and CLN8 diseases), gene therapy vector (for CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN10, and CLN11 diseases), and pharmacological drugs (for CLN1, CLN2, CLN3, and CLN6 diseases) have been evaluated for safety and efficacy in pre-clinical and clinical studies. Currently, cerliponase alpha for CLN2 disease is the only approved therapy for NCL. Lacking is any study of potential treatments for CLN4, CLN9, CLN12, CLN13 or CLN14 diseases. This review provides an overview of genetics for each CLN disease, and we discuss the current understanding from pre-clinical and clinical study of potential therapeutics. Various therapeutic interventions have been studied in many experimental animal models. Combination of treatments may be useful to slow or even halt disease progression; however, few therapies are unlikely to even partially reverse the disease and a complete reversal is currently improbable. Early diagnosis to allow initiation of therapy, when indicated, during asymptomatic stages is more important than ever.

PubMed Disclaimer

Similar articles

  • The Neuronal Ceroid Lipofuscinoses.
    Mole SE. Mole SE. In: Noebels JL, Avoli M, Rogawski MA, Vezzani A, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies. 5th edition. New York: Oxford University Press; 2024. Chapter 50. In: Noebels JL, Avoli M, Rogawski MA, Vezzani A, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies. 5th edition. New York: Oxford University Press; 2024. Chapter 50. PMID: 39637217 Free Books & Documents. Review.
  • Genetics of the neuronal ceroid lipofuscinoses (Batten disease).
    Mole SE, Cotman SL. Mole SE, et al. Biochim Biophys Acta. 2015 Oct;1852(10 Pt B):2237-41. doi: 10.1016/j.bbadis.2015.05.011. Epub 2015 May 27. Biochim Biophys Acta. 2015. PMID: 26026925 Free PMC article. Review.
  • Cell biology of the NCL proteins: What they do and don't do.
    Cárcel-Trullols J, Kovács AD, Pearce DA. Cárcel-Trullols J, et al. Biochim Biophys Acta. 2015 Oct;1852(10 Pt B):2242-55. doi: 10.1016/j.bbadis.2015.04.027. Epub 2015 May 8. Biochim Biophys Acta. 2015. PMID: 25962910 Review.
  • Therapeutic approaches to the challenge of neuronal ceroid lipofuscinoses.
    Kohan R, Cismondi IA, Oller-Ramirez AM, Guelbert N, Anzolini TV, Alonso G, Mole SE, de Kremer DR, de Halac NI. Kohan R, et al. Curr Pharm Biotechnol. 2011 Jun;12(6):867-83. doi: 10.2174/138920111795542633. Curr Pharm Biotechnol. 2011. PMID: 21235444 Free PMC article. Review.
  • Advances in the Treatment of Neuronal Ceroid Lipofuscinosis.
    Rosenberg JB, Chen A, Kaminsky SM, Crystal RG, Sondhi D. Rosenberg JB, et al. Expert Opin Orphan Drugs. 2019;7(11):473-500. doi: 10.1080/21678707.2019.1684258. Epub 2019 Nov 27. Expert Opin Orphan Drugs. 2019. PMID: 33365208 Free PMC article.
See all similar articles

Cited by

See all "Cited by" articles

References

    1. Schulz A, Kohlschütter A, Mink J, Simonati A, Williams R. NCL diseases—clinical perspectives. Biochim Biophys Acta. 2013;1832:1801–6. - PubMed - PMC
    1. Donsante A, Boulis NM. Progress in gene and cell therapies for the neuronal ceroid lipofuscinoses. Expert Opin Biol Ther. 2018;18:755–64. https://doi.org/10.1080/14712598.2018.1492544 . - DOI - PubMed
    1. Johnson TB, Cain JT, White KA, Ramirez-Montealegre D, Pearce DA, Weimer JM. Therapeutic landscape for Batten disease: current treatments and future prospects. Nat Rev Neurol. 2019;15:161–78. https://doi.org/10.1038/s41582-019-0138-8 . - DOI - PubMed - PMC
    1. Kohlschütter A, Schulz A, Bartsch U, Storch S. Current and Emerging Treatment Strategies for Neuronal Ceroid Lipofuscinoses. CNS Drugs. 2019;33:315–25. https://doi.org/10.1007/s40263-019-00620-8 . - DOI - PubMed - PMC
    1. Platt FM. Emptying the stores: lysosomal diseases and therapeutic strategies. Nat Rev Drug Discov. 2018;17:133–50. http://www.nature.com/articles/nrd.2017.214

Substances

LinkOut - more resources