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New Antitoxin Targets Many Pathogens

A team of researchers at Tufts University has developed a powerful and efficient way to weaken toxins and clear them from the body.

Toxins produced by dangerous bacteria such as Clostridium botulinum or certain strains of E. coli can cause serious damage or even death if allowed to take their course. Current strategies for combating these toxins involve the use of multiple antibodies derived from immune animals. Such therapies can pose health risks such as serum sickness and unknown viruses, and are expensive to produce. Other toxin-neutralizing approaches stop immediate illness but generally do not clear the toxin from the body.

Now scientists at Tufts’ Cummings School of Veterinary Medicine have developed a strategy in which a single, cloned antibody is directed to multiple places on the targeted toxin, resulting in a stronger attack on the toxin along with the ability to flush it from the system.

“So we’re getting the benefit of both neutralization and clearance but we’re doing it with much more simple and defined reagents,” explained lead researcher Charles Shoemaker, a professor of Biomedical Sciences in the Tufts Cummings School of Veterinary Medicine, in an interview with Food Safety News.

The study – published in PLoS ONE online journal earlier this year – focused on targeting botulinum neurotoxins, which cause paralysis, usually starting in the eyes and face and progressing down through the body. The toxin comes from Clostridium botulinum bacteria, which can be transmitted via food or open wounds, and is considered to be one of the most dangerous potential agents of bioterrorism.

The strategy developed by the team was able to prevent symptoms of botulism in infected mice, as well as tag the toxins for removal from the mice’s bodies.

Expanding to Combat Other Toxins 

This same strategy has also proved successful at combating other harmful toxins, such as those from pathogenic strains of E. coli and Clostridium difficile.

In the case of E. coli, which produces two types of harmful Shiga toxins, the technology permits neutralization and clearance of both toxins with a single molecule, resulting in a simple, streamlined treatment.

“With a single agent, we can target both toxins because we can link multiple different binding agents together like beads on a string,” says Shoemaker. “So we can have two toxin-neutralizing binding agents for both Shiga toxins 1 and 2 in the same molecule.”

These developments could be especially important because there is currently no approved therapy for Shiga toxin poisoning.

While other antitoxin treatments are already in clinical trials and will probably hit the market sooner, they will likely be more expensive and less effective, says Shoemaker, as most only neutralize and do not clear toxins, and require separate antibodies for Shiga toxins 1 and 2.

Moving the Solution from Lab to Market

How easy will it be to get these antitoxins out of the lab and into clinical use?

The good news is that the molecules are cheap and easy to develop, meaning that they can be mass produced at a low cost.

Since all of them use the same antibody, the only thing that needs to be produced from one toxin treatment to another are the binding agents that attach the antibodies to the toxins. These agents are “very quick to develop and very cheap to produce,” according to Shoemaker.

They are also extremely stable and have a long shelf life, he says.

The challenge in getting these antitoxins into treatment centers will be the ability to test them on humans.

Finding E. coli patients to administer antitoxins to requires waiting until an outbreak occurs, and even then there will be a limited number of test cases.

The anti-Shiga toxin strategy will also need a commercial supporter interested in investing the time and effort needed to see it through to the clinic.

The team’s botulism antitoxins have a better chance of being put to use sooner, since the government is likely to support their development as an anti-terrorism effort.

“There’s a lot of interest from the biodefense side so they may be the earlier applications over Shiga toxin,” says Shoemaker.

© Food Safety News