Developing Novel Therapies for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 7]: Opportunities From Restorative Neurobiology

Author:

Gharooni Aref-Ali1ORCID,Kwon Brian K.2,Fehlings Michael G.3ORCID,Boerger Timothy F.4ORCID,Rodrigues-Pinto Ricardo56ORCID,Koljonen Paul Aarne7ORCID,Kurpad Shekar N.4,Harrop James S.8,Aarabi Bizhan9,Rahimi-Movaghar Vafa10,Wilson Jefferson R.3ORCID,Davies Benjamin M.1ORCID,Kotter Mark R. N.1,Guest James D.11ORCID

Affiliation:

1. Neurosurgery Unit, Department of Clinical Neuroscience, University of Cambridge, UK

2. Vancouver Spine Surgery Institute, Department of Orthopedics, The University of British Columbia, Vancouver, BC, Canada

3. Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada

4. Department of Neurosurgery, Medical College of Wisconsin, Wauwatosa, WI, USA

5. Spinal Unit (UVM), Department of Orthopaedics, Centro Hospitalar Universitário do Porto - Hospital de Santo António, Porto, Portugal

6. Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal

7. Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

8. Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA

9. Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA

10. Department of Neurosurgery, Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran

11. Department of Neurosurgery and The Miami Project to Cure Paralysis, The Miller School of Medicine, University of Miami, Miami, FL, USA

Abstract

Study design Narrative review. Objectives To provide an overview of contemporary therapies for the James Lind Alliance priority setting partnership for degenerative cervical myelopathy (DCM) question: ‘Can novel therapies, including stem-cell, gene, pharmacological and neuroprotective therapies, be identified to improve the health and wellbeing of people living with DCM and slow down disease progression?’ Methods A review of the literature was conducted to outline the pathophysiology of DCM and present contemporary therapies that may hold therapeutic value in 3 broad categories of neuroprotection, neuroregeneration, and neuromodulation. Results Chronic spinal cord compression leads to ischaemia, neuroinflammation, demyelination, and neuronal loss. Surgical intervention may halt progression and improve symptoms, though the majority do not make a full recovery leading to lifelong disability. Neuroprotective agents disrupt deleterious secondary injury pathways, and one agent, Riluzole, has undergone Phase-III investigation in DCM. Although it did not show efficacy on the primary outcome modified Japanese Orthopaedic Association scale, it showed promising results in pain reduction. Regenerative approaches are in the early stage, with one agent, Ibudilast, currently in a phase-III investigation. Neuromodulation approaches aim to therapeutically alter the state of spinal cord excitation by electrical stimulation with a variety of approaches. Case studies using electrical neuromuscular and spinal cord stimulation have shown positive therapeutic utility. Conclusion There is limited research into interventions in the 3 broad areas of neuroprotection, neuroregeneration, and neuromodulation for DCM. Contemporary and novel therapies for DCM are now a top 10 priority, and whilst research in these areas is limited in DCM, it is hoped that this review will encourage research into this priority.

Funder

National Institute for Health Research

Cambridge University Hospitals NHS Foundation Trust

University of Cambridge

Publisher

SAGE Publications

Subject

Neurology (clinical),Orthopedics and Sports Medicine,Surgery

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