Anthrax toxin could be key to new pain therapies

Harvard Medical School scientists have found that certain elements in the toxin produced by anthrax bacteria can turn off the activity of brain neurons that transmit pain signals and suggest this could be a tissue new paradigm for future pain-relieving therapies.

The toxin of the disease can be deadly, but it works to block the sensation of pain

Anthrax toxin consists of several molecules secreted by anthrax bacteria. Each protein is non-toxic by itself, but when combined, they can be deadly. This new study aims to understand for the first time how these anthrax toxins affect nerve cells in the brain.

The common feature of anthrax is black skin lesions.

The study found that specific pain-sensing neurons in the dorsal root ganglia (DRG) appear to carry high-affinity receptors for binding to anthrax toxin. Through an impressive series of experiments, researchers have demonstrated exactly how two particular anthrax proteins alter signaling inside nerve cells.

There are two types of anthrax toxins - edema toxins and lethal toxins. Both toxins share an important protein, called PA (protective antigen). PA is likened to the "Troyan horse", helping to transport edema factor (EF) or death factor (LF) protein into cells.

New study convincingly demonstrates how edema toxins (including PAs and EFs) can selectively target and silence pain signaling neurons in the dorsal root ganglia. . Experiments on mice showed that when these two proteins were injected into the animals' spines, they effectively targeted certain nerve cells in the brain and blocked pain perception.

Dr. "This molecular platform that uses bacterial toxins to deliver substances into neurons and modulate their function is a novel way to target," said Isaac Chiu, senior investigator for the study. pain mediators".

Dr. Nicole Yang, co-author, explains: "We took parts of anthrax toxin and combined them with the protein we wanted it to transport. In the future, more proteins could be detected. varied to provide targeted treatments".

Of course, this type of research is very early and much more work will be needed before a potential new therapy moves from the lab to humans. But the researchers are confident that by delivering this edematous toxin to the brain via the spine, known as intramedullary administration, it will avoid potential toxicity problems in the rest of the body. . However, it is clear that further research is needed to better understand any broader effects this toxin may have directly on the brain.

To date, early indications of this toxin's action on the brain are very targeted, and there have been no indications in animal tests that there is a disruption to other mechanisms such as liver function. mobility. The researchers intriguingly hypothesize that this amazing specificity of toxin activity in the brain may be an evolutionary adaptation that helps anthrax bacteria evade detection in the organisms it infects. infected.

The common feature of anthrax is black skin lesions, which patients often describe as painless. The researchers speculate that this pain-blocking mechanism may explain the strange pain-reducing phenomenon. And this study is an example of how the natural world can help scientists develop new ways to treat pain.