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

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.

Structural Myelopathies

“…There is considerable interest in studying neuroprotective agents such as riluzole and cell-based therapies in patients with degenerative myelopathies. 38 OTHER CAUSES OF STRUCTURAL MYELOPATHY Mimics of myelopathy typically fall into two groups: disorders that have similar symptoms but discordant physical examination findings and disorders that have similar symptoms and similar examination findings. This section discusses other less common structural myelopathies as well as clinical entities that can have symptoms similar to those of myelopathy.…”

“…To this end, DTI imaging may offer a way to predict which patients are at risk for decline and may offer a more objective way to longitudinally assess nonsurgical therapies. There is considerable interest in studying neuroprotective agents such as riluzole and cell-based therapies in patients with degenerative myelopathies 38 …”

Prognostic analysis of traumatic spinal cord injury-related factors

“…The current treatment of spinal cord injury mainly adopts the strategy of stabilizing the condition, preventing further aggravation, and symptomatic treatment. The effect of retrograde therapy for neurological trauma is not satisfactory [4]. According to the results of previous investigations, only about 1% of SCI patients can recover to the normal level of neurological function, while up to 45% of patients are accompanied by severe neurological dysfunction [5].…”

Development of a core measurement set for research in degenerative cervical myelopathy: a study protocol (AO Spine RECODE-DCM CMS)

“…So far, AO Spine RECODE-DCM has established the top research priorities and agreed on a single definition and index term 4 8 21–32. It has also agreed on ‘what’ should be measured in DCM research: that is, a minimum data set, which is comprised core data elements (CDE) and a core outcome set (COS).…”