Pioneering the profiling of glycosaminoglycans in early cancer detection

Cancer is the second leading cause of death globally, though more and more patients are now surviving thanks to increasingly earlier detection and intervention. This requires the identification of reliable biomarkers that are analogous to the ‘canary in the mine’ – indicators of serious trouble ahead, but well before cancer symptoms are conclusive. Glycosaminoglycans, or GAGs for short, are novel biomarkers that have caught the attention of the biomedical research community.

GAGs are polysaccharides with wide-ranging roles in biology and health that have been implicated in processes that lead to disease development, such as cancer, but also respiratory failure and viral infections. Underpinning all GAG research is the need for a standardized measurement technology which has not been available – until now. Karl Bergman and Karin Mattsson are the Chief Executive Officer and Vice President of R&D respectively at pioneering Swedish diagnostics company Elypta. Working closely with Merck* as its contract manufacturing partner, Elypta has produced the first standardized extraction kit for full-spectrum human GAG quantification in body fluids, and it might just be a game changer in cancer research.

Innovation in GAG extraction and measurement

“The main goal at Elypta is to prevent cancer mortality by enabling earlier detection of cancer,” explains Bergman. “We think this can be achieved through our pioneering metabolism-based liquid biopsy rather than the genomic or proteomic approaches that are out there,” he says.

For many cancer indications, the global standard for diagnosis has been medical imaging and/or biopsy. However, these are not always useful when cancer symptoms are unclear and they additionally carry risks, high costs and inconvenience for patients. In such circumstances, technology providers are often looking for alternative, less invasive techniques. Elypta is currently developing a glycosaminoglycan kit for in vitro diagnostic use which aims to provide non-invasive, safe, and convenient means for detecting recurrence in kidney cancer patients.

For research use only and available now, Elypta has developed the MIRAM™ Glycosaminoglycan Kit. The kit enables accurate quantification of the comprehensive profile of glycosaminoglycans and can be used on a wide variety of body fluid samples including blood, urine, cell cultures and tissues, of which only small amounts are required, as Mattsson attests: “The analysis requires low sample volume and the kit is easy to use.”

The extraction kit works through an enzymatic digestion assay that breaks down GAGs into disaccharides. It combines ultra-high performance liquid chromatography (UHPLC) with electrospray ionization triple-quadrupole mass spectrometry (ESI-MS/MS) to accurately measure the concentration and structural composition of key GAGs: chondroitin sulfate, heparan sulfate and hyaluronic acid. This precision and efficiency allow for standardized performance and, longer term, permitting earlier detection and the potential to increase the chances of successful treatment. “Ultimately, we are doing this to enable in vitro diagnostic applications,” Bergman says. “That’s the goal, and in doing so it makes sense to strive for as great precision, robustness and reliability as possible,” he adds.

Choosing the right manufacturing partner

Whilst Elypta has a keen focus on product development, it makes use of the manufacturing expertise and experience provided by Merck, an arrangement that brings major benefits to a small company like Elypta, according to Mattsson. “Merck is a trusted partner when it comes to all the necessary documentation, such as validation plans, test methods for manufacturing and quality control,” she says. “We have a close and efficient collaboration with Merck."

While Merck has extensive manufacturing capabilities, it brings much more to the table, explains Dr. Yves Dubaquie, Head of Diagnostics Solutions at Merck. “We have a dedicated team, with R&D specialists that can help to develop a particular process and lock-down test specifications, and we have dedicated program managers that all have manufacturing backgrounds to help bring these programs forward.” All this expertise is wrapped into Merck’s quality system to allow it to support all manufacturers within this spectrum, a benefit that Bergman also acknowledges. “They are perfectly positioned to support us with the research needs we have during a long development project,” he enthuses. “For a small company working, with a company such as Merck provides credibility to what we’re manufacturing at an early stage and that can be quite important,” Bergman adds.

Research uses for GAG extraction technology

As a metabolism-based liquid biopsy approach, the Elypta MIRAM™ Glycosaminoglycan Kit can be used for biomedical research at all levels, including basic research into the role of GAGs in cancer initiation, evolution or progression. In the preclinical arena, it may be used to analyze GAGs in animal, cellular or xenograft models of cancer, while its clinical research applications include human cancer validation studies and the role of GAGs as biomarkers. “This is why we have made our kits available for research use. We recognize that there are many important questions in cancer that others are better positioned to address,” Bergman says.

Future developments

Bergman offers an insight into where Elypta is taking its technology. “Our first aim in in vitro diagnostic development is the creation of a test to determine recurring kidney cancer, where there are no molecular tests at the moment,” he says.

But there are many broader uses of the Elypta kit yet to be realized, as Bergman suggests. “What we need is more clinical and preclinical research to fully explore what the ‘GAG-ome’ can bring to cancer diagnosis and other disease areas. We are therefore inviting other researchers to make use of the kit to explore other research questions that we don’t focus on at present.”

For more information on Elypta's efforts to prevent cancer mortality by enabling earlier detection of cancer, see the related resource:

Video: Enabling earlier cancer detection with glycosaminoglycan profiling

In this video, Elypta's Karl Bergman, CEO, and Karin Mattsson, Vice President of R&D, talk about the first standardized service for full spectrum glycosaminoglycan quantification and how valued Merck's support has been throughout its development.

*The Life Science business of Merck operates as MilliporeSigma in the U.S. and Canada.