title: Viral vectors for therapy of neurologic diseases.
abstract: Neurological disorders - disorders of the brain, spine and associated nerves - are a leading contributor to global disease burden with a shockingly large associated economic cost. Various treatment approaches - pharmaceutical medication, device-based therapy, physiotherapy, surgical intervention, among others - have been explored to alleviate the resulting extent of human suffering. In recent years, gene therapy using viral vectors - encoding a therapeutic gene or inhibitory RNA into a "gutted" viral capsid and supplying it to the nervous system - has emerged as a clinically viable option for therapy of brain disorders. In this Review, we provide an overview of the current state and advances in the field of viral vector-mediated gene therapy for neurological disorders. Vector tools and delivery methods have evolved considerably over recent years, with the goal of providing greater and safer genetic access to the central nervous system. Better etiological understanding of brain disorders has concurrently led to identification of improved therapeutic targets. We focus on the vector technology, as well as preclinical and clinical progress made thus far for brain cancer and various neurodegenerative and neurometabolic disorders, and point out the challenges and limitations that accompany this new medical modality. Finally, we explore the directions that neurological gene therapy is likely to evolve towards in the future. This article is part of the Special Issue entitled "Beyond small molecules for neurological disorders".
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: sourav.rc@gmail.com.
authors.forename: Sourav R
authors.initials: SR
authors.lastname: Choudhury
authors.affiliation: Alzheimer's Disease Research Unit, Harvard Medical School & Massachusetts General Hospital, Charlestown, MA 02129, USA. Electronic address: ehudry@mgh.harvard.edu.
authors.forename: Eloise
authors.initials: E
authors.lastname: Hudry
authors.affiliation: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, USA. Electronic address: cmaguire@mgh.harvard.edu.
authors.forename: Casey A
authors.initials: CA
authors.lastname: Maguire
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA; Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: miguel.esteves@umassmed.edu.
authors.forename: Miguel
authors.initials: M
authors.lastname: Sena-Esteves
authors.affiliation: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, USA. Electronic address: breakefield@hms.harvard.edu.
authors.forename: Xandra O
authors.initials: XO
authors.lastname: Breakefield
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA. Electronic address: pag24@pitt.edu.
authors.forename: Paola
authors.initials: P
authors.lastname: Grandi
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000502:physiology / Q000627:therapeutic use*; D006801:Humans; D009422:Nervous System Diseases / Q000628:therapy*
keywords: Brain tumors; Gene therapy; Lysosomal storage diseases; Metabolic diseases; Neurodegeneration; Viral vectors