Neuronal Ceroid Lipofuscinosis: Potential for Targeted Therapy
- 1 January 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Drugs
- Vol. 81 (1), 101-123
- https://doi.org/10.1007/s40265-020-01440-7
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.This publication has 170 references indexed in Scilit:
- A Homozygous Mutation in KCTD7 Links Neuronal Ceroid Lipofuscinosis to the Ubiquitin-Proteasome SystemAmerican Journal of Human Genetics, 2012
- Strikingly Different Clinicopathological Phenotypes Determined by Progranulin-Mutation DosageAmerican Journal of Human Genetics, 2012
- Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosisHuman Molecular Genetics, 2012
- Synergistic effects of central nervous system‐directed gene therapy and bone marrow transplantation in the murine model of infantile neuronal ceroid lipofuscinosisAnnals of Neurology, 2012
- Imaging gene delivery in a mouse model of congenital neuronal ceroid lipofuscinosisGene Therapy, 2011
- Kufs Disease, the Major Adult Form of Neuronal Ceroid Lipofuscinosis, Caused by Mutations in CLN6American Journal of Human Genetics, 2011
- Parent-reported benefits of flupirtine in juvenile neuronal ceroid lipofuscinosis (Batten disease; CLN3) are not supported by quantitative dataJournal of Inherited Metabolic Disease, 2011
- Immunosuppression alters disease severity in juvenile Batten disease miceJournal of Neuroimmunology, 2011
- Survival advantage of neonatal CNS gene transfer for late infantile neuronal ceroid lipofuscinosisExperimental Neurology, 2008
- Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and miceJCI Insight, 2008