title: Neuronopathic lysosomal storage disorders: Approaches to treat the central nervous system.
abstract: Pharmacological research has always focused on developing new therapeutic strategies capable of modifying a disease's natural history and improving patients' quality of life. Despite recent advances within the fields of medicine and biology, some diseases still represent a major challenge for successful therapy. Neuronopathic lysosomal storage disorders, in particular, have high rates of morbidity and mortality and a devastating socio-economic effect. Many of the available therapies, such as enzyme replacement therapy, can reverse the natural history of the disease in peripheral organs but, unfortunately, are still unable to reach the central nervous system effectively because they cannot cross the blood-brain barrier that surrounds and protects the brain. Moreover, many lysosomal storage disorders are characterized by a number of blood-brain barrier dysfunctions, which may further contribute to disease neuropathology and accelerate neuronal cell death. These issues, and their context in the development of new therapeutic strategies, will be discussed in detail in this chapter.
authors.affiliation: Center for Rare Diseases, Horst Schmidt Kliniken, Department of Child and Adolescent Medicine, Ludwig-Erhard-Straße 100, 65199 Wiesbaden, D, Germany; University of Padova, Department of Women and Children Health, Via Giustiniani 3, Padova, Italy; Brains for Brains Foundation, Department of Women and Children Health, Via Giustiniani 3, Padova, Italy. Electronic address: maurizio.scarpa@hsk-wiesbaden.de.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Brains for Brains Foundation, Department of Women and Children Health, Via Giustiniani 3, Padova, Italy. Electronic address: cinzia.bellettato@brains4brain.eu.
authors.forename: Cinzia Maria
authors.initials: CM
authors.lastname: Bellettato
authors.affiliation: Center for Rare Diseases, Horst Schmidt Kliniken, Department of Child and Adolescent Medicine, Ludwig-Erhard-Straße 100, 65199 Wiesbaden, D, Germany. Electronic address: Christina.lampe@hsk-wiesbaden.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Lampe
authors.affiliation: Brains for Brains Foundation, Department of Women and Children Health, Via Giustiniani 3, Padova, Italy; Kings College London, Institute of Pharmaceutical Science, Franklin-Wilkins Building, Stamford Street, London SE1 9NH, UK. Electronic address: david.begley@kcl.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Begley
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism*; D016503:Drug Delivery Systems; D056947:Enzyme Replacement Therapy / Q000379:methods*; D006801:Humans; D057967:Infusions, Intraventricular; D060186:Infusions, Spinal; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D020140:Lysosomal Storage Diseases, Nervous System / Q000188:drug therapy* / Q000378:metabolism; D018832:Molecular Chaperones / Q000627:therapeutic use; D053758:Nanoparticles / Q000627:therapeutic use; D011994:Recombinant Proteins
chemical_list: D018832:Molecular Chaperones; D011994:Recombinant Proteins
keywords: blood–brain barrier; central nervous system; drug delivery; lysosomal storage disorders; neurodegeneration