The bacterium Clostridium botulinum produces the world’s most potent poison, which can cause paralysis, labored breathing, and death — it’s called botulism. The same toxin also smooths wrinkles in the skin at low concentrations because nature is weird like that. There’s an approved treatment for botulism, but it’s not perfect. Two different teams have devised a new way to treat botulism that could more effectively clear the dangerous toxin from cells and tissues, and it relies on a modified version of the toxin itself. It won’t do anything for your crow’s feet, though.
The botulinum toxin is so deadly because it’s adept at slipping into nerve cells where it blocks the release of a vital neurotransmitter called acetylcholine. The most common way to contract botulism is by eating improperly stored food that has allowed the Clostridium bacteria to proliferate. While relatively few people get botulism in the US — there are about 200 cases each year — it’s more common in the developing world, and the early symptoms are often misdiagnosed. There’s also the potential that Clostridium botulinum could be used as a bioweapon.
Current treatments can clear botulism toxin from the bloodstream, but it can’t do anything about the toxins that have already infiltrated cells. That’s where the work from Boston Children’s Hospital and the Czech Republic’s National Institute of Mental Health could make a difference. Both studies adopted similar approaches of linking an antibody to modified botulinum molecules, essentially using botulinum as a transport mechanism for the antibodies.
In the immune system, antibodies are produced to help the body tell the difference between “self” and “something else that ought not to be there.” If an antibody sticks to something foreign, it tags it for removal by the immune system. Some antibodies can also neutralize molecules and other proteins simply by sticking them to block their functions. The teams engineered antibodies that can neutralize botulinum and stuck them to modified versions of the toxin that don’t cause disease but can still enter cells.
The teams tested their treatments in several animal models including mice and macaques. They report that animals receiving the treatment survived exposure to dangerous levels of botulinum toxin, and the controls did not. The antibody-linked botulinum didn’t contribute to any additional toxic effects, either. Although, at high concentrations, the neutered toxin can still cause paralysis.
Because most cases of human botulism involve a reservoir of toxin in the gut (i.e. food poisoning), the standard treatment will probably still be necessary. However, the addition of botulism-linked antibodies could help pull critically ill patients back from the brink by neutralizing the toxins already in their cells. This work is still preliminary, though. It will take years of additional work before the FDA will allow these to be used in humans.
Top image credit: Sicai Zhang/Dong Lab, Boston Children’s Hospital
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