Venom Immunotherapy

By Kevin Ritchart

Until recently, the concept of venom immunotherapy was primarily associated with stinging insects, but recent developments are redefining this field of study. Found to be much more than a treatment for bee stings, venom immunotherapy as it relates to spiders, snakes and snails was among the topics covered at the 60th Annual Meeting of the Biophysical Society last year.

A peptide toxin called ProTx-II, which was extracted from the Peruvian green velvet tarantula, has shown the potential through research to be an effective, non-addictive alternative to traditional painkillers.

ProTx-II works by binding the pain receptor located within the membrane of neuronal cells. The exact peptide-receptor binding site within the neuronal cells is unknown, as is the importance of the cell membrane in blocking pain signals.

A 2015 Australian study found that seven compounds extracted from spider venom have shown the ability to block a protein instrumental in sending pain signals to the brain. The poison used by arachnids to control their prey contains molecules that can impair the proteins responsible for carrying pain signals between nerves and the brain. If these compounds can be isolated and properly controlled, spider venom could prove to be an effective treatment tool for chronic pain sufferers.

A protein called Nav1.7 is believed to be the primary channel by which pain signals are transmitted in humans. Australian scientists screened the venom of 206 spiders to find the seven compounds that proved effective in blocking Nav1.7 pain signals during lab tests. In all, 40 percent of the venom examined as part of the study contained peptides capable of blocking the Nav1.7 pathway.

Jamming Pain Signals

The venom of the black mamba snake is considered to be among the deadliest in the world, but the identification of multiple proteins contained in the venom of the dangerous reptile has proven effective in eliminating pain – in some cases, with as much potency as morphine.

Scientists have discovered proteins contained within venom that serve to effectively jam the channels that allow ions to flow across the membranes of neurons. This chemical cross-chatter in and out of cells is what allows neurons to send messages to the brain and elsewhere in the body. Jamming these communication channels open or closed is what disrupts communication – thereby interrupting the transmission of pain signals – from the site of the pain to the brain and back.

To test this theory further, scientists collected venom from 40 species of scorpions, spiders, sea anemones and snakes, separated them into their component molecules and poured them onto frog cells in a Petri dish to observe the response. The scientists wanted to find out whether the acid-sensing ion channels of the frog cells, which play a key role in the transmission of pain signals, were blocked as a result of the venom.

Scientists observed that two proteins from the black mamba – named mambalgin-1 and mambalgin-2 – did block the pain signals in a Petri dish. The proteins had the same effect on human cells.

Breaking Through Barriers

Another example of scientists turning to unconventional sources to find inspiration for new painkillers is Prialt, which is based on a component from the venom of a marine snail. Prialt is an incredibly powerful painkiller that’s sometimes given to patients when morphine proves ineffective.

One of the reasons Prialt is not more popular is that it’s difficult to administer. Because it doesn’t pass the blood-brain barrier, Prialt must be administered via an injection to the spinal column. The blood-brain barrier is a kind of membrane that prevents most compounds in the blood from entering the brain, but Prialt can’t ease a patient’s pain if it doesn’t get to the brain.

Scientists have been exploring different ways of getting Prialt across the blood-brain barrier without having to administer spinal injections. Lab tests using a cell-penetrating peptide to deliver the Prialt have proven successful, but further testing will be needed to determine whether the drug is effective once it breaks the blood-brain barrier in this manner before the drug can be injected directly into the blood stream or eventually taken in pill form.