On the trail of a new antidote for the black widow bite

The Mediterranean black widow (Latrodectus tredecimguttatus) is one of the most dangerous spiders in the world and can also be found in Croatia. Bite cases are rarely fatal, as there is an antidote derived from horse antibodies, but can it also be produced from human antibodies?

Consequences of a Bite

Although venomous, the black widow is not considered aggressive unless threatened. With its bite, it injects the protein alpha-latrotoxin (α-LTX) into the victim, which acts on the nervous system, specifically on neuromuscular signal transmission. It leads to the release of transmitters from acetylcholine and adrenergic nerve endings. The venom also contains cytotoxic enzymes such as collagenase, hyaluronidase, and esterase. The bite results in a condition, rarely fatal, known as latrodectism. Symptoms include intense pain and muscle cramps, nausea, vomiting, and excessive sweating, while the bite site shows redness, swelling, and cyanosis.

The antidote derived from horses

The clinical treatment of latrodectism is primarily symptomatic and involves the parenteral administration of opioids in combination with benzodiazepines. However, administration of the antidote is more effective.The traditional method of its production involves injecting alpha-latrotoxin into a horse, causing the horse to develop antibodies against it, which are then isolated. When these antibodies are introduced into the human body after a bite, they enhance the immune response and prevent the effect on the nervous system. However, it should be emphasized that the effect may not be the same for every individual, as our immune system sometimes recognizes the antidote as something foreign. In such cases, potentially fatal allergic reactions, known as “serum sickness”, can occur.

Use of human antibodies

To avoid potential complications, German scientists conducted a study using human IgG antibodies produced in the laboratory. They used methods such as phage display, ELISA testing, protein purification, SDS-PAGE electrophoresis, immunoblot analysis, and lyophilization. They tested over 10 billion different antibodies to determine if any could bind to and neutralize alpha-latrotoxin, and it turned out that 45 of them could. Among these, the MRU44-4-A1 antibody stood out for having the highest neutralization capability.

Pros and cons

The main advantage to highlight is that antibodies could be produced on demand and relatively quickly. This would eliminate the entire process of administering the toxin to the horse and waiting for the horse to produce the antibodies. Additionally, since the antibodies would contain components that are exclusively human, the likelihood of immune reactions is reduced.

So far, the new antidote has only been tested on mouse tissue cultures in the laboratory. It is expected that it will take several more years before human testing becomes possible. During the research, it was observed that there is a difference in the potency of the venom depending on the manufacturer, so this factor must also be taken into account during testing.

Translated by: Josip Kokanović