Deadly Neurotoxin from Pufferfish Could Create a Generation of Non-Addictive Pain Relievers.
Tetrodotoxin (TTX) is the most potent natural neurotoxin known to humanity. It is produced in the bodies of marine animals such as pufferfish, snails, octopuses, salamanders, frogs, and worms. For over a century, scientists worldwide have attempted to synthesize TTX in laboratory settings to explore and harness the power of this mysterious biochemical. It seems that a research team from New York University (NYU) has made significant progress in this area.
Tetrodotoxin (TTX) commonly found in pufferfish – (Photo: Whiteway/iStock)
In a recently published study, researchers revealed a 22-step process using biologically active TTX that is highly efficient and can be produced from readily available materials. They claim to have discovered the “easiest” method for synthesizing TTX. The research was published in the journal Science.
Dirk Trauner, a chemistry professor at NYU and one of the study’s authors, stated, “Our project is not the first synthesis of tetrodotoxin; however, this method is the most efficient to date, improving the technological level by 30 times.”
TTX is often considered a mystery by many scientists because they are still uncertain about how animals like pufferfish produce and store this toxin in their bodies. Furthermore, there remains a significant mystery surrounding the chemical’s properties used for purposes beyond self-defense. Professor Trauner and his team believe that TTX could be regarded as a “keystone molecule” due to its role in defining predator-prey relationships within ecosystems.
Additionally, it is thought to act as an appetite stimulant in some organisms. As a potent neurotoxin that causes paralysis, TTX can block sodium channels in nerve cell membranes and disrupt signaling within nerve circuits. This brings us to the primary reason why scientists have been “fascinated” by TTX for so long.
The researchers claim that TTX’s ability to block sodium channels holds secrets related to developing a new class of effective painkillers.
“The medical demand for painkillers with new mechanisms of action is enormous. TTX has the interesting property of blocking nerve signals. These signals are essential for the sensation of pain in humans, and thus TTX is considered a promising lead for developing the next generation of non-addictive pain medications,” Trauner remarked.
Tetrodotoxin is found in the liver and reproductive organs of marine animals. Japanese scientist Dr. Yoshizumi Tahara first isolated TTX in 1894 and confirmed it again in 1909. Since then, scientists have been studying and attempting to synthesize this chemical in laboratory settings.
However, creating a stable and pure version of TTX has been a challenge for biochemists due to its complex structure and instability. Although scientists have previously managed to synthesize TTX, most of those neurotoxins were either unstable or less effective. Additionally, many of those methods could not be scaled up due to complications involved.
“The main challenge in synthesizing TTX is its high chemical complexity, instability, and the challenges posed during purification and isolation. This is reflected in previous syntheses that require more steps and are overall less efficient,” Professor Trauner explained.
Interestingly, the TTX synthesis method proposed by NYU researchers starts with a glucose derivative, consists of only 22 steps, and yields an impressive 11% efficiency. Professor Trauner and his research team claim that this method is now the most efficient and perhaps the only scalable approach for producing TTX and its derivatives. Researchers will now use this foundation to delve deeper into the pain-relieving properties of this neurotoxin.
