Your browser doesn't support javascript.
loading
On-demand cell-autonomous gene therapy for brain circuit disorders.
Qiu, Yichen; O'Neill, Nathanael; Maffei, Benito; Zourray, Clara; Almacellas-Barbanoj, Amanda; Carpenter, Jenna C; Jones, Steffan P; Leite, Marco; Turner, Thomas J; Moreira, Francisco C; Snowball, Albert; Shekh-Ahmad, Tawfeeq; Magloire, Vincent; Barral, Serena; Kurian, Manju A; Walker, Matthew C; Schorge, Stephanie; Kullmann, Dimitri M; Lignani, Gabriele.
Afiliación
  • Qiu Y; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • O'Neill N; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Maffei B; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Zourray C; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Almacellas-Barbanoj A; Department of Developmental Neurosciences, Zayed Centre for Research Into Rare Disease in Children, GOS-Institute of Child Health, University College London, London, UK.
  • Carpenter JC; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Jones SP; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Leite M; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Turner TJ; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Moreira FC; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Snowball A; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Shekh-Ahmad T; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Magloire V; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Barral S; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Kurian MA; Department of Developmental Neurosciences, Zayed Centre for Research Into Rare Disease in Children, GOS-Institute of Child Health, University College London, London, UK.
  • Walker MC; Department of Developmental Neurosciences, Zayed Centre for Research Into Rare Disease in Children, GOS-Institute of Child Health, University College London, London, UK.
  • Schorge S; Department of Neurology, Great Ormond Street Hospital for Children, London, UK.
  • Kullmann DM; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Lignani G; Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Science ; 378(6619): 523-532, 2022 11 04.
Article en En | MEDLINE | ID: mdl-36378958
ABSTRACT
Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity. Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and "healthy" surrounding or intermingled neurons. We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy. We used an immediate early gene promoter to drive the expression of Kv1.1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity. Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors. Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Epilepsia / Canal de Potasio Kv.1.1 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Science Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Epilepsia / Canal de Potasio Kv.1.1 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Science Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido