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Great expectations: virus-mediated gene therapy in neurological disorders
  1. Didu Kariyawasam1,2,
  2. Ian E Alexander3,4,
  3. Manju Kurian5,6,
  4. Michelle Anne Farrar1,2
  1. 1 Neurology, Sydney Children's Hospital Randwick, Randwick, New South Wales, Australia
  2. 2 School of Women's and Children's Health, UNSW Medicine, University of New South Wales, Sydney, New South Wales, Australia
  3. 3 Discipline of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
  4. 4 Gene Therapy Unit, Children's Medical Research Institute, Westmead, New South Wales, Australia
  5. 5 Neurosciences Unit, Institute of Child Health, University College London, London, UK
  6. 6 Neurology, Great Ormond Street Hospital for Children, London, UK
  1. Correspondence to Dr Michelle Anne Farrar, Neurology, Sydney Children's Hospital Randwick, Randwick, NSW 2031, Australia; m.farrar{at}


Gene therapy (GT) has tremendous potential for the treatment of neurological disorders to transform patient care. The successful application of virus-mediated GT to treat spinal muscular atrophy is a significant milestone, serving to accelerate similar progress in a spectrum of neurological conditions, with more than 50 clinical trials currently underway, across neurodevelopmental, neurodegenerative, muscular dystrophy, epilepsy, chronic pain and neoplastic diseases. This review provides an overview of the key features of virus-mediated GT, paradigms of delivery and dosing, potential risks and highlights ongoing research to optimise safe and effective delivery of vectors into the nervous system. Examples of the application of GT in various neurological diseases alongside clinical development challenges will be presented. As the development and translation of GTs gain pace, success can only ultimately be realised for patients following implementation in the health system. The challenges and controversies of daunting costs, ethics, early diagnosis and health system readiness will require innovative pricing schemes, regulatory policies, education and organisation of a skilled workforce to deliver of high-quality care in clinical practice as we prepare for advanced therapeutics in neurology.

  • virology
  • neurogenetics
  • clinical neurology
  • neuromuscular

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  • Contributors DK and MAF planned the manuscript. DK executed and prepared the first and subsequent drafts of the manuscript. DK, MAF, IEA and MK contributed to manuscript revision. All authors read and approved the submitted version.

  • Funding DK acknowledges funding from the RTP Scholarship, University of New South Wales and The Freedman Family Foundation Scholarship, Sydney Children’s Hospital Foundation. MAK is funded by an NIHR Research Professorship (176009), Sir Jules Thorn Award for Biomedical Research (549424) and MRC DPFS Award (545926).

  • Competing interests MF has received compensation as a member of the scientific advisory board for Biogen, Roche and AveXis. DK has received reimbursement for attending symposia, sponsored by Biogen. IA has received compensation for the cost of participation on a Novartis advisory panel.These funding bodies had no role in the manuscript design, preparation of the manuscript or decision to publish.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.