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The Sophiris Boondoggle

By DrKSSMDPhD, November 13, 2015

A brief column, if I may, to capture the teachable moment offered to us by the release of 52-week data from Sophiris ($SPHS).

Longer-term readers recall that we first introduced Sophiris as a long investment idea on 30 November 2014. The company had taken an unusual toxin, called aerolysin, from the freshwater bacteria Aeromonas that, when activated, associates with six other protein monomers like it to make a heptameric pore in the nearest eukaryotic (animal, plant, fungus) cell. Blammo! This is a defense mechanism (and not in the Freudian sense) for the bacteria.

The pore does to the attacked cell what an al Qaeda bomb did to the USS Cole in that Yemeni harbor. Cells live in part on the basis of their surrounding membrane’s ability to maintain chemical differences between cell interior and cell exterior. The hole so blown in the cell causes a rush of ions and proteins both into and out of the cell, and it dies (whether by necrosis or by apoptosis isn’t clear to me from the science).

Sophiris scientists wanted a wanted a way to make a cloned aerolysin that could only be activated, only undergo self-assembly into a heptamer, in prostate tissue. Prostate cells all make prostate specific antigen, which is a serine proteinase with vague similarities to the digestive enzyme chymotrypsin. Sophiris scientists clone-spliced a protein strand onto one end of aerolysin monomer to act as a bait for PSA, which would then snip it and free the monomers to roll up into a doughnut shape to make a pore. They dubbed this protein topsalysin. If you could inject this into multiple sites in the prostate gland, the idea was Swiss-cheese-like lacunes would form in the gland where tissue died, whereupon surrounding tissue would respond in sinkhole fashion, freeing up the urethra.

The prostate gland, which may be a more specialized version of an ancient mammalian scent gland, exists solely to facilitate reproduction. Because the gland surrounds the urethra, it forms a strait or bottleneck. With a facilitating state of mind and physiology enabled by blood testosterone levels, the male urogenital tract, all of it, becomes aroused. The glandular apparatuses in the prostate begin elaborating a viscous fluid that becomes a delivery medium for spermatozoa about to be vigorously off-loaded. Evolution doesn’t care how long you live so long as you reach its goalpost of reproducing yourself, and the prostate generally behaves well until ...

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