The new antidote passed the first animal experiments. If the drug works in humans, it would save the patient from months of intensive care.
Small in doses it smoothes wrinkles and relieves muscle cramps, in larger doses it blocks breathing and leads to death.
Botulinum is the world’s most potent neurotoxin, against which scientists have now developed an antidote.
The antidote was developed from botulinum itself. Like the original toxin, it is able to penetrate nerve cells and carry antibodies with it.
If the drug works in humans, this would be the first time the drug can prevent paralysis caused by botulinum toxin. Patients would be spared even months of lying in a ventilator, according to a publication published in the journal Science research.
Botulinum toxin is the world ‘s strongest poison in terms of dose size. A millionth of a gram can be enough to kill a person.
When botulinum is used in small doses topically, it works in the treatment of both beauty and disease. It temporarily paralyzes the facial muscles and thus prevents skin wrinkles.
In neurology, botulinum is used especially in the treatment of muscle spasms and stiffness. The toxin paralyzes the meat locally, allowing it to relax. Botulinum can be given, for example, to a child with cp disability to treat limb stiffness or to treat muscle stiffness caused by a blood clot.
When injected into the bladder, botulinum reduces urinary incontinence and excessive sweating in the sweat glands. In addition, botulinum can be used to treat migraines and eye diseases.
“Last over the years, the toxin has also been found to have an analgesic effect. More and more new uses are constantly being found, ”says the professor Miia Lindström From the Faculty of Veterinary Medicine of the University of Helsinki.
He runs a laboratory specializing in botulinum research, which is the only one in his field in Finland. In addition to basic research, the group is developing antibodies and tests for neurotoxin.
According to Lindström, the use of botulinum in medical procedures is safe, but in incompetent hands, working with a neurotoxin involves its own risks.
If the botulinum injection hits the wrong place, the toxin will paralyze the wrong muscle for several months. Thus, beauty treatment can cause partial paralysis of the drooping eyelid or face.
In overdose, the neurotoxin causes botulinum poisoning, or botulism, which at worst leads to quadriceps paralysis and death.
Typically botulinum poisoning occurs instead of an injection at the dining table. Produces botulinum toxin Clostridium botulinum bacterium, the spores of which occur in both soil and water bodies.
If the spores end up in the anaerobic conditions favorable to them, the spore shell breaks down and a viable cell emerges. As it proliferates, the cell spreads toxic botulinum around it.
Canned and vacuum-packed fish products are an example of favorable conditions for spores. Spores migrate from soil or water to fish and vegetables, where they are relatively harmless to a healthy person.
But if a food containing spores is packaged in an oxygen-free state and then stored at room temperature, the spores can turn into a bacterial crop that spreads the toxin.
The greatest risks are associated with foods stored at home, as sporicidal heating may be deficient.
If a poison has been formed, it is difficult to detect it in food. Botulinum toxin is completely odorless and tasteless.
Bacterial spores can also end up in the blood from a wound and a dirty needle. Botulism does occur to some extent among injecting drug users, Lindström says.
“In addition, poisoning occurs as an intestinal infection in infants, where the bacterium gets to colonize the baby’s intestines.”
Although the patient is conscious, he may no longer be able to communicate due to the progressive paralysis condition.
In the body botulinum penetrates nerve muscle terminals and breaks down proteins needed for neurotransmitter release. As a result, the nerve impulse is broken and the muscle is paralyzed.
It takes a few hours to a few days for symptoms to appear. The first symptom of food poisoning is usually vomiting.
The paralysis begins in the face. It manifests as visual disturbances and difficulty speaking and swallowing. The paralysis progresses to the limbs and eventually to the internal organs.
“Poisoning becomes life-threatening when botulinum paralyzes the respiratory muscles,” says Lindström.
According to him, identifying botulism can be difficult for nursing staff. The patient may behave like a drunk. Although the patient is conscious, he may no longer be able to communicate due to the progressive paralysis condition.
Patient can be saved if the cause of the symptoms is identified in time. Diagnosis requires laboratory tests on both the patient’s digestive tract and the food suspected of guilt.
Poisoning is now treated with antibodies produced from horse serum that destroy the toxin from the bloodstream and prevent the disease from progressing. However, current antidotes do not last until the nervous system.
This is problematic because by the onset of symptoms, some of the poison has already ended up out of reach of antibodies. Then the body’s function must be supported by a ventilator until new neuromuscular terminals are created to replace the destroyed ones.
“In mild cases, the patient recovers completely, but in more severe symptoms, the patient may have permanent neurological symptoms.”
New the antidote works more cunningly. A team at New York Medical University prepared the drug from botulinum toxin itself by harnessing the poison as a carrier of antibodies.
The researchers modified botulinum toxin to be genetically safer. Modified botulinum is not able to break down proteins responsible for the passage of nerve signals, but it is able, like a toxin, to penetrate the patient’s nervous system with antibodies.
It chases its deadly counterparts all the way to the nerve cells and takes them off their weapons.
“In other words, we just developed a Trojan horse,” said led the research team Konstantin Ichtchenko To the journal Science.
The antidote has not been developed as before in animals, which researchers say is more ethical and faster.
Development work seemed promising, but animal experiments showed that even at high doses, genetically modified botulinum could also be lethal. Thus, a group at Boston Children’s Hospital diluted the drug with a different modification of botulinum.
“A new antidote can help patients recover faster than before. The drug not only stops the spread of the disease by removing the toxin from the bloodstream, but could alleviate the symptoms of paralysis that have already begun by neutralizing the toxin in the nervous system, ”says the university lecturer. Katja Selby and postdoctoral researcher François Douillard From the University of Helsinki.
According to them, it was also important in the studies that two types of antibodies could be transported with the same drug. Thus, one drug is simultaneously effective against poisoning caused by two different types of botulinum, perhaps even more in the future.
In addition, the antidote has not been developed as before in animals, which researchers say is more ethical and faster. The possibility of allergic reactions is also lower with the new drug.
“When an antibody is developed in an animal, it is in contact with allergens. The new drug therefore has a lower risk of sudden hypersensitivity reactions. ”
Medicines successfully tested in mice, guinea pigs, and macaque monkeys.
Mice were injected with a lethal dose of botulinum, and some received antidote nine hours after dosing. The mice that received the highest dose were able to exercise as early as six hours after treatment. Untreated mice had difficulty breathing and had to be stopped.
Of the monkeys, all drug-treated animals were alive ten days after treatment, whereas untreated monkeys were to be sacrificed in less than four days.
Next, the groups will seek approval for their drugs from the U.S. Food and Drug Administration (FDA). Despite promising results, much development work remains to be done.
Molecular biologist at the University of California James Marks pointed out to Science that levels of botulinum in animal experiments were small compared to poisonings found in humans, where botulinum can end up in the gut slowly into the bloodstream for days or weeks.
“Drug development is a long and rocky road. But that’s where it starts, ”Marks said.
In the United States, about 200 cases of botulism are reported each year.
Today botulism is rare due to better food storage. In Finland, four cases of poisoning have been reported in the last twenty years.
In 2011, two people received poisoning of an Italian canned olive, and one of them died. The previous cases of botulism are from 2006.
“Milder cases may not have been diagnosed correctly, in which case some of the cases may have been left in the dark,” Lindström says.
In many European countries, the incidence is somewhat higher. In France, Germany, Italy and Poland, botulism has been caused by meat products. In the United States, about 200 cases of botulism are reported each year.
Botulism epidemics are rare. The most recent is from 2006, when more than 200 people in Thailand fell ill after eating bamboo shoots containing the poison.
For the slightest despite cases of poisoning, the development of new antidotes to botulism is important. Botulinum is considered one of the most potential biohazards. One gram of botulinum sprayed as an aerosol would be enough to kill 1.5 million people.
Botanic toxin has been classified by the U.S. Agency for Disease Control and Prevention (CDC) as the most dangerous Class A based on its potential biohazard potential. The European Medicines Agency (EMA) also classified the substance as one of the most dangerous bio-threats.
The Department of Health and Welfare (THL) defines a biohazard as a mass illness caused by a microbe or biological material. Mass illness becomes a threat when the normal resources of a hospital or hospital district are not sufficient to manage it.
The idea of botulinum toxin arose during the First World War.
The idea of botulinum toxin born in during World War I, when an attempt was made to purify the poison into a respirable aerosol or powder to be soaked in liquids.
During World War II, the United States even designed by smuggling botulinum toxin by Chinese prostitutes in pin-sized capsules. The contents of the capsule were to be poured into the drinking glasses of Japanese officers.
In the future botulinum is increasingly being used to save people instead of killing them. The effect of neurotoxin is now being studied in the treatment of depression and asthma, among others.
It all started with sausage
■ Botulinum toxins have plagued humanity, especially since we started storing food, such as ham, fish and vegetables.
■ The name of the poisoning comes from the Latin word botulus for sausage, as initially most of the poisonings were caused specifically by sausage.
■ Medicinal powders dried from blood sausages by poppies killed people even before botulinum contact with poorly preserved food was identified. In 19th-century Germany, people were even warned not to eat smoked blood sausages because of the food poisoning they caused.
■ Cause of poisoning found finally a German doctor Justinus Kernerin thanks to clinical trials. A doctor named Wurst-Kerner suggested a couple of hundred years ago that sausage poison extract could be used as a medicine in various conditions of nervous overstimulation.