Sea cucumber – a source of valuable polysaccharides?

It has been almost a year since my last post, order which was shortly after Biomarine 2014 in Cascais, rx Portugal. I’m heading to Biomarine 2015, this year in Wilmington NC, which is an exciting opportunity to meet marine biotechnology companies from around the world.

In that last year the work we have done on Sea cucumber polysaccharides was published in The Journal of Biological Chemistry (DOI:10.1074/jbc.M114.572297). This was a nice piece of work involving collaboration with six different academic groups. Too many authors to name-check here, but the publication grew out of our long-term collaboration with Dusan Uhrin, at University of Edinburgh, and Haris Panagos his PhD student was first author. This kind of collaboration is key to GlycoMar’s business model, enabling the early stage research that we can then take into commercial development.

The paper described the structure and biological properties of fucosylated chondroitin sulphate (fCS) extracted from sea cucumber body wall. These molecules are unusual variants of chondroitin sulphate, the glycosaminoglycan found in human cartilage and extracted from shark and other animal cartilages to provide the nutraceutical supplement chondroitin, which is often combined with glucosamine from crustacean shell. fCS has been known for around 20 years, and can be isolated from a wide range of sea cucumber species; to quote from our paper:

“Sea cucumbers have been used as a traditional tonic food in many Asian countries for centuries, with the major edible parts being the body walls, which are predominantly comprised of collagen and acidic polysaccharides. ……In addition to being a culinary delicacy, sea cucumbers have attracted considerable attention from researchers due to a range of the biological activities of fCSs that can be isolated from their tissues in high yields. The fCSs isolated from a variety of sea cucumbers were reported to possess anticoagulant, antithrombotic, anti-inflammatory, anti-HIV and metastasis-blocking properties.”

Interest in these molecules is reflected by a large number of papers being published around the world, particularly in Asia.

Our own work was able to show specific aspects of the conformation of the molecule that is responsible for the molecular interaction with one of the well known binding targets – the selectin family of adhesion molecules which are important in inflammatory cell recruitment and trafficking. This kind of early mechanism of action work is invaluable for pharmaceutical discovery.

 

Discovery to development

fCS exemplifies the challenge and opportunity offered by novel marine natural products: how to move beyond early stage research into product development.

Clearly the molecules have potential value, but the journey to make a drug or other product based on fCS has only just begun (see our web page for typical drug discovery timelines). Our next step is explore methods for production of high purity natural and mimetic fCS variants; once we have these we can explore the biological profile of this chemical space and identify the best candidate. At the same time we can develop the routes for chemical synthesis or semi-synthesis of these molecules, in order to have a sustainable and high quality production system suitable for a future pharmaceutical product.

The next steps in drug development will take a few years, and continue to rely on collaborations with specialist academic and commercial partners. At the same time fCS might offer a short- to medium-term opportunity for a nutraceutical product? This will rely on availability of a sustainable (preferably farmed) source of sea cucumbers in quantities suitable for commercial extraction and marketing. Maybe fCS would bring some innovation into the joint-care market dominated by glucosamine and chondroitin?

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