The tarantula's bite that could stop pain - Spider venom could hold the key for a new medication for chronic pain. Viviane Richter reports.
Neither a tarantula’s painful bite nor a sea snail’s lethal sting sound all that pleasant – or useful – for humans.
But venom from the poisonous pair could lead to next-generation
painkillers, thanks to a group of scientists from Australia’s University
of Queensland. They discovered how a toxin found in a tarantula’s venom
delivers its blow, and with that knowledge created a promising new drug
candidate to treat chronic pain.
To catch a fast-moving meal, venomous animals such as the tarantula
sting, injecting a cocktail of paralysing peptides into their prey. At
molecular scale, these peptides find and dock to tiny so-called “sodium
ion channels” dotted along the outer membrane of nerve cells.
Some of these channels are responsible for transmitting nerve signals
to muscles. Once the venom peptides are latched on, nerve cells stop
firing, preventing prey from moving or escaping.
But not all channels are the same – some are only responsible for
transmitting pain signals to the brain. This has prompted scientists to
develop venom peptides as chronic pain medication. The key is making it
selective – a new painkiller is little use if it ends up paralysing a
patient.
The Queensland team analysed and modelled how a toxin from the
Peruvian green velvet tarantula, called ProTx-II, docks to its channel
target.
The team’s data suggests that before the peptide locks on, it’s
“sucked in” by the molecules in the membrane around the channel. Only
when several peptide molecules congregated, simulations showed, did the
peptides locked in the right orientation to block their target channel.
“Our results show that the cell membrane plays an important role in
the ability of ProTx-II to inhibit the pain receptor,” author Sónia
Troeira Henriques said.
Using this information, the team are now designing potential drugs that are more likely to find a painkilling target.
The researchers started by modifying a peptide called MfVIA, isolated from the venom of the predatory sea snail Conus magnificus, known as the “magnificent cone”.
The team synthesised modified versions of the sea snail peptide,
designed to latch more strongly to the area around its ion channel
target. One of these new peptides “showed a striking improvement in
selectivity” over other channel types, the authors stated.
The peptide has also already been effective in treating pain in
animal models, the team added. The findings were presented in the Biophysical Society’s 60th Annual Meeting.
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