Fred,
Well tetrodoxin is at very least plausible as a treatment for chronic pain. There's a lot of focus on sodium channels as a key factor in chronic pain, although more effort seems focused on the subset of these that are tetrodoxin resistant. But there are some indications that tetrodoxin susceptible sodium channels are also implicated (see abstract at end).
Biotech Jim would likely be the best person to comment on the science.
The obvious objection to tetrodoxin is of course that it's lethal in tiny quantities - it's about 10,000 times more toxic than cyanide. So the key question is whether there is any therapeutic window at all between an effective dose and a lethal dose. If it worked, it wouldn't be the first naturally occurring very lethal substance that has found a medical use - botulinum toxin is another good example.
I generally have a very negative reaction to penny biotechs - it's hard enough developing a drug with $250m in the bank, let alone with $13m which is what they seem to have had at the end of December 2003. But taking a quick look at this, it doesn't seem to be a scam. It looks pretty promotional, but that's par for the course for a penny biotech. They do have a European partner, which does reduce the risk some.
Bottom line after a very quick look - not someplace I'd put money personally, but perhaps not unreasonable for someone looking to play biotech roulette.
Here's the abstract I mentioned:
Pain. 2004 Apr;108(3):237-47. Related Articles,Links
Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain.
Black JA, Liu S, Tanaka M, Cummins TR, Waxman SG.
Department of Neurology and Paralyzes Veterans of America, Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale University School of Medicine, New Haven CT 06510, USA. joel.black@yale.edu
Nociceptive neurons within dorsal root ganglia (DRG) express multiple voltage-gated sodium channels, of which the tetrodotoxin-resistant (TTX-R) channel Na(v)1.8 has been suggested to play a major role in inflammatory pain. Previous work has shown that acute administration of inflammatory mediators, including prostaglandin E2 (PGE2), serotonin, and adenosine, modulates TTX-R current in DRG neurons, producing increased current amplitude and a hyperpolarizing shift of its activation curve. In addition, 4 days following injection of carrageenan into the hind paw, an established model of inflammatory pain, Na(v)1.8 mRNA and slowly-inactivating TTX-R current are increased in DRG neurons projecting to the affected paw. In the present study, the expression of sodium channels Na(v)1.1-Na(v)1.9 in small (< or = 25 micromdiameter) DRG neurons was examined with in situ hybridization, immunocytochemistry, Western blot and whole-cell patch-clamp methods following carrageenan injection into the peripheral projection fields of these cells. The results demonstrate that, following carrageenan injection, there is increased expression of TTX-S channels Na(v)1.3 and Na(v)1.7 and a parallel increase in TTX-S currents. The previously reported upregulation of Na(v)1.8 and slowly-inactivating TTX-R current is not accompanied by upregulation of mRNA or protein for Na(v)1.9, an additional TTX-R channel that is expressed in some DRG neurons. These observations demonstrate that chronic inflammation results in an upregulation in the expression of both TTX-S and TTX-R sodium channels, and suggest that TTX-S sodium channels may also contribute, at least in part, to pain associated with inflammation.
Peter |
