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A systematic review of adeno-associated virus gene therapies in neurology: the need for consistent safety monitoring of a promising treatment
  1. Rebecca H Horton1,
  2. Dimah Saade2,
  3. Theodora Markati1,
  4. Elinor Harriss3,
  5. Carsten G Bönnemann4,
  6. Francesco Muntoni5,
  7. Laurent Servais1,6
  1. 1 Department of Paediatrics, University of Oxford, Oxford, UK
  2. 2 Division of Neurology, University of Iowa, Iowa, USA
  3. 3 Bodleian Health Care Libraries, University of Oxford, Oxford, UK
  4. 4 National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA
  5. 5 Dubowtiz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital, UK, London, UK
  6. 6 Neuromuscular Reference Center, Department of Paediatrics, CHU of Liège, Liège, Belgium
  1. Correspondence to Dr Laurent Servais, Department of Paediatrics, University of Oxford, Oxford OX1 2JD, UK; Laurent.servais{at}


Adeno-associated virus (AAV) gene therapies are generating much excitement in the rare disease field, particularly for previously untreatable neurological conditions. Efficacy has been claimed for several gene therapy products and the number of trials is rapidly increasing. However, reports of severe treatment-related adverse reactions are emerging, including death. There is still insufficient knowledge about their aetiology, prevention and treatment. We therefore undertook to systematically review publicly available data on AAV gene therapies in order to collate existing information on both safety and efficacy. Here, we review emerging efficacy reports of these novel therapies, many of which show promise. We also collate an increasing number of adverse reactions. Overwhelmingly, these results make a case for unified reporting of adverse events. This is likely to be critical for improving the safety of these promising treatments.

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  • Contributors LS, FM, CB and RHH conceptualised the study. EH, DS and RHH completed the literature search. TM and RHH performed the data extraction and risk of bias assessment. RHH and LS wrote the paper.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests FM has received honoraria for scientific advisory boards from Novartis Gene Therapies Inc., Biogen, Novartis, PTC, Roche, Pfizer, Dyne Therapeutics and Sarepta. LS has received consulting fees from Sarepta, Pfizer, Roche, Affina, Renegex Bio, Audentes, Evox Therapeutics and Novartis. He has received honoraria from Sarepta, Roche, Audentes and Novartis. He is the secretary of the World Muscle Society. DS, EH, TM, RHH and CGB have no conflicts of interest to declare. TM is a scholar of the Onassis Foundation (Scholarship ID: F ZQ 040-1/2020-2021).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.