Non-toxic versions of botulism toxins can deliver therapeutic antibodies to treat botulism

Taking advantage of the chemical properties of botulism toxins, two teams of researchers have developed non-toxic versions of these fertilizers that can deliver therapeutic antibodies to treat botulism, a disease that can be fatal with very little of permitted treatments.

The research, conducted in mice, guinea pigs, and nonhuman primates, suggests that the toxin derivatives may one day offer a platform to quickly address established cases of botulism and target hard-to-reach molecules. within neurons. Botulism occurs as a result of bacterial toxins called botulinum neurotoxins (BoNTs), which are the most potent known toxins in humans.

BoNTs work by interfering with and damaging neurons that coordinate movement, leading to paralysis that requires intensive care and may survive for months. There is an urgent need for treatments that can quickly reverse paralysis, but it is difficult to develop treatments for pre-existing cases as it is challenging to neutralize BoNTs with once-in-one therapy that the toxins have entered neurons.

In the first study, Shin-Ichiro Miyashita and colleagues combined different sections of two BoNTs called BoNT / X and BoNT / A, resulting in a chimney molecule that is both toxic and acts as a high-molecule. drug delivery platform.

In particular, the researchers combined a neuron-targeting domain of BoNT / A with another range of BoNT / X capable of delivering therapeutic molecules into neurons.

Miyashita et al. found that their approach rapidly delivered antitoxin antibody into neurons and neutralized both BoNT / A and BoNT / B neurotoxins in mice, returning paralysis within a few hours of -time. Taking a similar approach, Patrick McNutt and colleagues performed a nontoxic BoNT derivative invention that safely neutralized BoNT / A within neurons.

Their treatment also reduced paralysis and strengthened survival in mice, guinea pigs, and nonhuman primates that were exposed to lethal amounts of BoNT / A. ”This platform offers a shape-shifting approach. adaptive for precise treatment that may be adapted to various presynaptic diseases, ”says McNutt et al.