Discovering epigenetic biomarkers of chronic back pain

Professor Laura Stone from the University of Minnesota Medical School has been studying the neuroscience of pain for 25 years. The Stone Lab focuses particularly on back pain and DNA methylation as its epigenetic modulator. Genevia Technologies has been providing them with bioinformatics support, with the aim of detecting patterns of DNA methylation associated with low back pain.

Professor Laura Stone

– My background is very much not in bioinformatics so it’s been very helpful to partner with Genevia because I’m able to focus on the biology, says Dr. Stone.

When Dr. Stone first learned about Genevia, she was in the midst of moving her lab to a new location. After relocating, they decided to use Genevia as an external bioinformatics service provider.

– I was trying to start a lab during Covid. I couldn’t hire anyone and we were not supposed to go on site but we had all these datasets, so this was just perfect timing.

Genevia has been working on multiple datasets with the Stone group. The projects have been pilot studies, the results of which are used in grant applications to enable larger future studies. Dr. Stone appreciates the help she has received with the grant applications – and the letters of support from Genevia's team and CSO, Professor Matti Nykter in particular.

One of the projects aimed at understanding the pathology of the spine of chronic back pain patients. The study was performed with human intervertebral discs collected over several years. Degeneration of intervertebral discs can cause chronic back pain. To understand the degenerative process, genome-wide DNA methylation measurements were carried out, comparing the discs of patients with chronic back pain to those of transplant donors as controls.

Another project focused on intervertebral disc degeneration in mouse models, again comparing degenerating discs to healthy ones.

– Scientifically, it’s interesting to understand the process of intervertebral disc degeneration and learning more about it could eventually help us do something to slow it down or at least make it less painful.

They are also interested in biomarkers for back pain.

– At the moment there are no objective biomarkers for pain. The gold standard in the field is asking the individual how much pain they have. Ultimately, the most important thing is how the person feels, but it impairs our ability to perform clinical studies since we do not have a marker to help us independently validate the effectiveness of a drug, for example. There are no biomarkers to help us predict whether someone with acute back pain will develop chronic pain or recover. If we could identify who is at a greater risk to develop chronic pain, we could theoretically intervene early.

– We think that these patterns, DNA methylation signatures, might be a very useful tool to develop biomarkers. We started initially looking at blood, but more recently, with Genevia’s help, we have moved to saliva since it is easier to access than blood.

Saliva has already shown its biomarker potential in a pilot study. Saliva samples from individuals with back pain and those without were tested and compared, and a potential signature identified. Stone has grant applications in place to pursue this work as well.

Genevia has also helped in analyzing saliva samples from patients with acute back pain, comparing individuals who went on to develop chronic pain to those who recovered. Again, the initial results are promising, suggesting that it might be possible to predict the risk of developing chronic pain, at least to some extent.

Flexible service and clear communication

The upcoming projects of the Stone Lab aim at studying epigenetic signatures in animal models and, specifically, looking at the central nervous system and the impact that chronic pain has on it. From previous studies, the research team knows that animals experiencing chronic pain have changes in DNA methylation in the cortex in the frontal part of the brain. This is where many of the higher cognitive functions, including experiencing pain, take place. Dr. Stone plans to take a multiomics approach to study the brain, with measurements of DNA methylation, RNA expression, and protein expression as well. She looks forward to continuing this work with Genevia.

Here is how Dr. Stone describes the collaboration with Genevia:

– I really appreciate the regular meetings and being kept up to date and having very easy access to everything, especially the descriptive reports. I also appreciate the project manager Maria Liivrand’s responsiveness and the clarity regarding schedules, for instance.

– Another thing that has been really nice is the flexibility. I think we have been working together now for over 1.5 years, and instead of working intensely for just a couple of months, we have been able to spread the support flexibly out where we need it.

– Overall, I’m extremely happy. The way everything is organized is very clear. I would definitely recommend Genevia to a colleague, and I have actually already done so.

– Genevia is doing a great service. It really is a smart approach, and the service is definitely needed. There are so many of us biologists who take advantage of these big data approaches – and data that already exists – but have no idea how to deal with all that information. I think it is brilliant that there is a place to go where you can get that bioinformatics expertise on an as-needed basis, instead of spending years gaining those skills yourself.

The Stone lab of the University of Minnesota Medical School