Could pufferfish posoin used as an anesthetic drug? Indeed, a new and impressive study, led by scientists at Boston Children’s Hospital, has developed a new method to tame one of the most potent toxins in the world, tetrodotoxin, which is commonly found in pufferfish. The research demonstrates a way to control the spread of the toxin and take advantage of it in an effective local anesthetic that can numb target regions for up to three days.
Tetrodotoxin is a somewhat notorious poison, known to kill hundreds of people. In Japan, a plate of sashimi, made from a kind of puffer fish known as fugu, is so controlled that there are strict regulations on its service. Chefs must train for at least three years, and obtain a license, before they are allowed to serve the dish. If improperly prepared, the dish can be easily contaminated with tetrodotoxin, quickly poisoning hungry diners.
Tetrodotoxin is such a potent toxin because of its incredibly efficient ability to induce paralysis. It is exactly this mechanism that has attracted scientists seeking to develop new forms of analgesics and anesthetic agents. The challenge of taking advantage of this toxin is to find a safe way to administer it in a specific area of the body and control the volume of release.
The new research describes a slow-release formulation that binds tetrodotoxin particles to a biodegradable polymer that degrades at a slow, controlled rate. This allows the release of tetrodotoxin in a localized area at a safe speed.
“One lesson we learned is that with our previous administration systems, the drug can leak too quickly, which leads to systemic toxicity,” explains Daniel Kohane. “In this system, we gave him an intravenous amount of tetrodotoxin that would be enough to kill a rat several times if it was given in the unlinked state, and the animals did not even seem to notice.”
To add to the localized efficacy of the technique, the researchers incorporated a compound called chemical permeation enhancer, which helps tetrodotoxin to easily permeate nervous tissue. This addition allows the toxin to enter more specifically into the local tissue, which means that a lower dose may be as effective as a higher concentration.
“With the enhancer, drug concentrations that are ineffective become effective, without increasing systemic toxicity,” says Kohane. “Every piece of drug you put in the packages is as strong as possible.”
Until now the technique has only been validated in animal tests. However, the first results are incredibly positive. In addition to being safe and non-toxic, the composition of the polymer can be modulated to control the rate of release and duration of anesthesia. In the rat models, the sciatic nerve was effectively blocked for a few hours to three days, depending on the polymer backbone used. Kohane suggests that in humans this duration could theoretically extend up to several weeks, depending on the condition to which it is directed.
“We could think of very long nerve block durations for patients with pain from cancer, for example,” says Kohane. «Certainly for days, and maybe for weeks.»
There is still much work ahead for the researchers before this innovation is translated to humans, but the first indications are promising that this technique can be extended effectively to human treatment. Considering the devastating opiate crisis that is taking place all over the world, any new way of treating chronic pain could be of great help, and this novel approach to a local anesthetic offers a new and convincing way to tackle group block specific nerves.