14 DAY TRIAL // A new study made by a team at the University of Wisconsin School of Medicine and Public Health (SMPH) and Scripps Research Institute explains how the botulinum toxin can inactivate nerve cells.
The toxin first attaches to a receptor on the surface of a neuron, then searches for a second type of receptor that is nearby. From the second receptor, it can enter the neuron and break signaling proteins. This way, tiny amounts of botulinum can cause general paralysis and even death through respiratory failure.
The botulinum-producing bacteria (photo) that grow in soil can be found inside cans of food that were improperly processed. "The toxin has to bind to the neuron it wants to poison. This is a snapshot of the first stage of that poisoning" says botulinum expert Edwin Chapman, UW-Madison professor of physiology and a Howard Hughes Medical Institute investigator.
The investigation found a short section on the protein receptor as the exact spot where botulinum toxin grips the cell immediately before entering it. The research could have several practical applications. Botulinum toxin is a potential biological weapon, so the U.S. Military needs to encounter anti-toxins to protect soldiers, a more approachable task with the new knowledge.
The findings could also improve treatments that use the toxin to block nerve signals. The treatments "are not just for wrinkles. People with paralysis get spasms in the muscles that are shut off, and this could solve that. In a wide variety of dystonias, where spasms can cause really severe pain, this can relax the muscles", said Chapman. "If a mutated toxin was made to attach to the mutated receptor, the combination might target botulinum toxin against over-active cells in the body," Chapman suggests.
Using genetic engineering, "you might be able to sensitize whatever cell you want to the toxin," he says. Such a treatment could slow mucus production in the lungs of cystic fibrosis patients, or attack hyperactive cells in a wide range of other disorders. The toxin is only able to attach to active neurons. "If the synapse between two nerve cells is not active, all the receptors will be hiding inside the cells. But a synapse that controls a very important muscle must be firing all the time, and it will be exposing more receptors, and the toxin will therefore target them", said Min Dong from the research team. "Botulinum toxin only goes where it can be effective. It's like a smart bomb."