A compound called pateamine A, derived from a Fiordland marine sponge, can prevent cancer-induced muscle wasting, or cachexia, say a group of Canadian researchers. Although high doses are known to be toxic, low doses of pateamine A inhibit the action of enzymes that cause muscle wasting, they reported in Nature Communications (June 12, 2012) . Cachexia often affects people with cancer and Aids. It doesn’t just affect quality of life – it’s the cause of 30% of all cancer-related deaths. With no approved drugs to treat cachexia, patients diagnosed with the condition are sent to palliative care.
“They start losing muscle, including that which is in the lungs, and they eventually die by asphyxia,” explains Imed Gallouzi, the paper’s senior author. The discovery of a possible way to treat the condition is a big breakthrough. Pateamine A’s bioactive properties were first reported in 1991 by Peter Northcote, now at Victoria University’s school of chemical and physical sciences. Northcote was a post-doctoral fellow at the University of Canterbury, working with natural products chemists John Blunt and Murray Munro, when he isolated and described the compound. The pateamine came from a brownish blobby marine sponge, Mycale sp, found at a depth of 10-20m, clinging to the vertical submarine cliffs in the black waters of Thompson Sound.
The Mycale sponge has so far been the source of several new cytotoxins, which are substances toxic to living cells, with potential as cancer treatments. Before pateamine, there was mycalamide A – which didn’t get to human trials because it was too toxic – found in Mycale living in Otago Harbour. In 2002, Northcote and his colleagues isolated peloruside A and B from Mycale growing in Pelorus Sound. Peloruside also proved to be a potent cytotoxin, acting as a protein synthesis inhibitor, but efforts to grow sufficient sponges to supply a pharmaceutical company with 20g of the precious extract to test were foiled when the entire aquaculture fell prey to an army of hungry nudibranchs, or sea slugs.
Finding, describing, testing and then synthesising new compounds is a lengthy process, but some drugs derived from marine sponges are already in use. AZT, which is used to treat HIV infection, and the herpes treatment Aciclovir, are both derived from compounds first isolated from a Caribbean marine sponge in the 1950s. So, what is it about sponges – a very ancient and diverse phyllum – that make them such a great source of novel compounds? “They haven’t got much else to defend them,” says Northcote. “They’re soft, easy to eat and they’re sessile – they can’t escape predation.” There is also huge competition for space on rocky reefs and, as well as deterring predators, the toxins in the sponges might help them compete for space with other reefdwelling species. “There’s so much we don’t know about why they produce these compounds, but we assume it’s some sort of defensive role.”
One of the interesting characteristics of sponges is that in some species “up to 30% of the biomass of the organism can be bacteria”, says Northcote. By looking at the genetics of the sponges and the genetics of the symbiotic bacteria, and creating taxonomic trees, scientists have determined that the relationship between the sponges and the bacteria is likely to have been established hundreds of millions of years ago. This relationship could be key to the interesting compounds found in sponges. Northcote recently isolated zampanolide, a known bioactive compound, from sponges collected around the Tongan islands. He is now working with the Samoan Government to set up a programme to examine Samoan sponges for biologically significant compounds.
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