By Miguel Ángel Huerta Martínez - The Conversation
What if I told you that pufferfish could help us fight the pain associated with cancer? This animal is a fascinating being and not only for its aesthetics and morphology, which has made it the protagonist of films, but also for its medicinal properties associated with a substance it produces: tetrodotoxin.
A journey through Asia in search of pufferfish
First, we'll embark on a journey through the Asian continent, where we'll have the opportunity to eat its meat, considered a delicacy. But be careful, our lives could be at risk. Pufferfish make a potentially deadly toxin, tetrodotoxin. In fact, a few milligrams would be enough to kill him.
So how do we eat this? For centuries, Asians have developed specific culinary techniques to inactivate the toxin so that it can be safely tasted. In a modest restaurant in the Haedomari market in the coastal town of Shimonoseki, Japan, chef Saito Hamada shows us how he detoxifies fugu – as they call it there – using the migaki technique.
Pufferfish has medicinal properties associated with a substance it produces: tetrodotoxin. Hal Beral/Getty Images
Despite the widespread popular experience in the consumption of this fish and the knowledge of the poison it produces, annually there are hundreds of poisonings associated with tetrodotoxin. Hamada warns us to only consume fugu meat in certified establishments that guarantee proper processing. In fact, in order to be able to cook it legally, you need a license obtained after several years of training.
After tasting pufferfish in all its culinary modalities, we return to Europe where, curiously, there have also been cases of poisoning.
Good news from Granada
To expand our knowledge about the therapeutic applications of tetrodotoxin, we will now travel to Spain. On the top floor of the Faculty of Medicine of the University of Granada, one of the tallest buildings in the city, we meet José M. Baeyens and Francisco R. Nieto, professors of the Department of Pharmacology.
In their office, with Sierra Nevada in the background, they tell us that they have been investigating the possible usefulness of tetrodotoxin as an analgesic in a model of neuropathic pain (that which occurs when there is damage to the nervous system) induced by chemotherapy in experimental animals (preclinical trials), obtaining very promising results.
In fact, a few years ago they participated in the patent of this molecule for the treatment of neuropathic pain induced by antineoplastic chemotherapy (which prevents cell proliferation).
To date, the efficacy of tetrodotoxin in preclinical models of neuropathic pain is very strong and has been confirmed by numerous groups from different corners of the world. As for its clinical evidence, focused on cancer-related pain, it is more modest but robust, as confirmed by several phase II and III clinical trials.
Cancer Pain and Its Treatment with Tetrodotoxin
Cancer-related pain is a complex, heterogeneous and very common phenomenon. It may be due to the tumor growth itself or its treatment with surgery, radiation therapy, or chemotherapy. It usually has a high neuropathic component, which makes its treatment difficult to manage.
In particular, neuropathy induced by cancer chemotherapy is a real headache for patients and doctors. Few drugs work and none are specific for this problem, as most are antidepressants or antiepileptics that have shown moderate efficacy and produce numerous undesirable effects.
In this context, there is a need for new analgesics to treat cancer-related pain. And this is where tetrodotoxin comes into the picture, the clinical development of which is at an advanced stage. In fact, a recent meta-analysis in which I participated concluded that it is effective in treating cancer-related pain without increasing serious adverse effects.
"Its clinical utility is exciting: it has shown efficacy in a type of pain that is particularly difficult to treat, peripheral neuropathy associated with chemotherapy," says Professor Nieto. Professor Baeyens adds: "There are also clinical trials showing effectiveness in patients with cancer-related pain, a more heterogeneous condition with a very high prevalence."
However, these clinical results are preliminary and need to be confirmed with trials involving a larger number of patients.
A phase III clinical trial is currently underway to justify the marketing request and the results will be known soon. If approved by regulatory agencies, it would be the first drug developed specifically for chemotherapy-associated peripheral neuropathy and a great joy to so many patients who would see their lives drastically improved.
One more example that nature is amazing and that almost everything in life can have a solution, even the most complex pain. And thanks to this research, we are getting closer and closer to eliminating it.