The RECODE-DCM initiative calls upon the global community of healthcare professionals working with Degenerative Cervical Myelopathy (DCM), and individuals living with DCM, to come together to solve the Top 10 Research Priorities — ten critical questions that are relevant to the whole community.
In this blog focusing on Research Priority 2: Natural History, we will hear about the work of Esmee Dohle, a final-year medical student and neurobiology supervisor at the University of Cambridge.
We welcome comments from our community on our RECODE-DCM blog posts. Please share your perspectives by emailing recode@myelopathy.org — we’re listening!
As the most common spinal cord condition worldwide, it is clear that DCM deserves more research attention. But how should this research be carried out? In general, studies tend to use animal models to investigate the pathophysiology of disease processes: the ‘why’ of a disease. However, alongside this, human spinal cord tissue represents a unique opportunity to study the disease in its natural context, enabling a better understanding of the underlying mechanisms and the development of more effective treatments.
We carried out a systematic review [1] into studies which used human spinal cord tissue to investigate histological features of myelopathy – in other words, we found and read all of the studies which put spinal cord tissue of real patients who had suffered with myelopathy under the microscope. In many ways, the studies echoed findings from animal models, with common features including loss of neurons, axons and demyelination, thereby confirming the validity of such models.
However there were some notable differences: the location of changes was seen to be different; human studies tended to report necrosis as a cause of cell death whereas animal studies tended to report apoptosis; and also, gliosis was more commonly reported in human studies. The exact reasons for these differences are uncertain, and in some cases (e.g. necrosis versus apoptosis) may simply relate to differing definitions of ‘cell loss’.
However, the review really highlights an opportunity: we found reports from only 150 patients, with very limited clinical information to explore the implications of spinal cord changes (i.e. how bad was their DCM, how was it managed, how did it relate to their imaging findings?). Animal models can offer DCM science much; for example, such models allow conditions to be manipulated to explore novel treatments. However, by necessity, animal models involve simplifications of disease factors, such as where or how the spinal cord compression is occurring, and for how long. Diseases are also often modelled in young animals, whereas DCM and perhaps DCM vulnerability changes with age. This means important insights may be overlooked.
Unlocking the aetiology of DCM is a critical research priority, fundamental to informing clinical care and identifying new treatments. A recent high quality study has been able to combine insights from animal models and human tissue [2].
So through this blog I pose two questions.
- To those who live with DCM, what would you think about leaving your spinal cord to research (when you don’t need it any more)?
- To scientists, what do you think are the opportunities that could come from spinal cord tissue, and how do we make it a reality?
Through this blog I wish to call for more scientists to join the RECODE-DCM community to work on the Top 10 Research Priorities.
To join the RECODE-DCM community, please sign up.
About the Author: Esmee Dohle
Hello everyone, I am Esmee Dohle, working at the University of Cambridge. I have experience of both pre-clinical research (involving electrophysiology and optogenetics) and clinical research (systematic review into myelopathy, and large retrospective study on inflammatory markers and frailty in stroke).
I became interested in RECODE-DCM and Myelopathy.org after meeting patients with myelopathy as a medical student, and realising the toll the disease takes on patients’ lives. With a lot of help from senior researchers, I was able to carry out my own research into myelopathy. I am planning to continue research in neurology and hope to carry this forward into the future..
References
- Dohle, E., Beardall, S., Chang, A. et al. (2023) Human spinal cord tissue is an underutilised resource in degenerative cervical myelopathy: findings from a systematic review of human autopsies. Acta Neurochir 165(5): 1121-1131
https://doi.org/10.1007/s00701-023-05526-5 - Badhiwala, J.H., Ahuja, C.S., Akbar, M.A. et al. (2020) Degenerative cervical myelopathy — update and future directions. Nat Rev Neurol 16: 108–124.
https://doi.org/10.1038/s41582-019-0303-0