Pharmaceuticals Pharmaceuticals
Marine sponge yields potential cystic fibrosis drug
Latonduine A, originally isolated from marine sponges off the coast of Indonesia, has shown promise as a
possible therapeutic for cystic fibrosis.
By Tyler Irving
Posted January 2013
A chemical isolated from marine sponges has shown surprising activity in both cell and animal models of cystic fibrosis, and could become the basis for a new therapeutic.
Cystic fibrosis results from a mutation in the gene for a membrane protein called the cystic fibrosis transmembrane conductance regulator (CFTR), which transports chloride ions in and out of epithelial cells. Although there are many possible mutations, the most common one results in misfolded CFTR becoming stuck in the cell’s internal machinery. A team led by David Thomas in the department of biochemistry at McGill University is using high-throughput screens to search for molecules which might get CFTR past that roadblock and out to the cell surface.
One of the screens was run on a collection of 720 extracts put together by University of British Columbia chemist Raymond Andersen, who for decades has been isolating novel compounds from marine sponges. The McGill team scored a hit with a compound called latonduine A, named after the island of Latondu in Indonesia where the sponges that produce it are found. “We found the latonduines years ago, but they had previously shown no biological activity,” says Andersen. “It was quite remarkable that they were so active in these assays.” Not only does latonduine A get CFTR to the surface in cell-based assays, it also provides up to 9 per cent correction in mouse models of cystic fibrosis. “That’s as good as anything we’ve seen, and including other people’s molecules,” says Graeme Carlile, a post-doctoral research associate in Thomas’s lab and lead author of the group’s latest paper, published in Chemistry and Biology.
Future work will be needed to determine if more active variants of latonduine A can be made, as well as to nail down the exact mechanism. Interestingly, preliminary tests of latonduine A in combination with other potential CFTR correctors have shown an additive effect. “There may be two separate flaws in the folding,” says Carlile, “So it might be better to produce two molecules instead of one.”
Photo credit: Raymond Andersen
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