Gene Therapy and Spinal Fusion: Systematic Review and Meta-Analysis of the Available Data.

Abstract

Objective

To analyze the extant literature describing the application of gene therapy to spinal fusion.

Methods

A systematic review of the English-language literature was performed. The search query was designed to include all published studies examining gene therapy approaches to promote spinal fusion. Approaches were classified as ex vivo (delivery of genetically modified cells) or in vivo (delivery of growth factors via vectors). The primary endpoint was fusion rate. Random effects meta-analyses were performed to calculate the overall odds ratio (OR) of fusion using a gene therapy approach and overall fusion rate. Subgroup analyses of fusion rate were also performed for each gene therapy approach.

Results

Of 1179 results, 35 articles met criteria for inclusion (all preclinical), of which 26 utilized ex vivo approaches and 9 utilized in vivo approaches. Twenty-seven articles (431 animals) were included in the meta-analysis. Gene therapy use was associated with significantly higher fusion rates (OR 77; 95% confidence interval {CI}: [31, 192]; P < 0.001); ex vivo strategies had a greater effect (OR 136) relative to in vivo strategies (OR 18) (P = 0.017). The overall fusion rate using a gene therapy approach was 80% (95% CI: [62%, 93%]; P < 0.001); overall fusion rates were significantly higher in subjects treated with ex vivo compared to in vivo strategies (90% vs. 42%; P = 0.011). For both ex vivo and in vivo approaches, the effect of gene therapy on fusion was independent of animal model.

Conclusions

Gene therapy may augment spinal fusion; however, future investigation in clinical populations is necessary.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1016/j.wneu.2024.03.174

Publication Info

Cottrill, Ethan, Zach Pennington, Nathan Sattah, Crystal Jing, Dave Salven, Eli Johnson, Max Downey, Shyni Varghese, et al. (2024). Gene Therapy and Spinal Fusion: Systematic Review and Meta-Analysis of the Available Data. World neurosurgery, 186. pp. 219–234.e4. 10.1016/j.wneu.2024.03.174 Retrieved from https://hdl.handle.net/10161/31384.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Varghese

Shyni Varghese

Laszlo Ormandy Distinguished Professor of Orthopaedic Surgery

Shyni Varghese has a triple appointment in the Duke departments of Biomedical Engineering, Mechanical Engineering and Materials Science, and Orthopaedic Surgery. She is the first MEDx Investigator.

A leader in the field of biomaterials and stem cells, Varghese will develop her research at Duke in three major areas:

  • Musculoskeletal tissue repair
  • Disease biophysics, and
  • Organ-on-a-chip technology


A new initiative of the Pratt School of Engineering and Duke School of Medicine, Duke MEDx seeks to enhance and form new collaborations between doctors and engineers.

Rocos

Brett Rocos

Assistant Professor of Orthopaedic Surgery

I joined the team at Duke University Health from London, UK, where I was a Consultant Adult and Paediatric Spine Surgeon at Barts Health NHS Trust and Honorary Consultant Senior Lecturer at Queen Mary University of London. I completed my surgical training in in the South West of the UK and at the University of Toronto, and am fellowship trained in adult spine surgery, paediatric spine surgery, orthopaedic trauma surgery, research and healthcare management.

I am driven to support patients at every stage of their care, from clinic assessment, through surgery to discharge. Making sure that every person, adult, child, family or friend understands what’s wrong, helping them to choose the right treatment for them, and what the recovery will be like is an important priority.

My research activity focusses on finding effective new treatments for spinal disorders and bringing them to patients. Focusing on spinal deformity, I have led investigations in the UK, Canada and the USA, and I sit on the Global AO Knowledge Forum for Deformity and the Research Grants Committee at the Scoliosis Research Society. I have lectured in North America and Europe about the treatment of spine disorders for the Scoliosis Research Society, Global Spine Congress, AO Spine and Eurospine, and I have worked hard to produce research that improves the care for spine patients wherever they live. Lastly, I review for several orthopaedic journals and I am Deputy Editor of the Bone and Joint 360, a leading publication with a global readership.

Richardson

William James Richardson

Professor of Orthopaedic Surgery
  1. Current research includes investigation of biomechanical aspects of cervical injury with head impact. This involves cadaveric work with high-speed photography and load cells to ascertain the mechanism for spinal fractures.

    2. An animal model is being used to evaluate the biomechanics of cervical laminectomy versus laminoplasty compared to the normal spine. A portion of the animals are developing myelopathy secondary to instability after the surgical procedure and this is being evaluated with MRI scanning as well as mechanical and radiographic testing.


    3. Studies are being performed to develop an impedance pedicle probe to aid safe insertion of pedicular instrumentation in the lumbar spine. Ongoing studies are being performed to define the optimal frequency for the probe to yield the most sensitive and specific device. Hopefully this will lead to development of a device for human use. Studies will compare impedance probe to currently used EMG techniques to see if combing them will lead to greater sensitivity and specificity.

    4. Studies are being completed on testing particular pull-out strength and doing a multi-varied analysis looking at size of the pedicle and bone density by two different techniques.

    5. Current work is ongoing to develop an outcomes instrument and database to be used in the outpatient setting for patients with spinal complaints, both cervical and lumbar. The device will be used to evaluate clinical effectiveness for a variety of treatments for spinal conditions and to look at patient satisfaction issues.

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