New possibilities for the medical use of botulinun toxin A1

PSI researchers have discovered a surprising trick that could expand the possibilities for medical use of botulinun toxin A1, better known under the name Botox, as an active agent. They have developed antibody-like proteins that speed up the enzyme's effect on the transmission of nerve signals. This suggests that Botox might, for example, be able to relief pain more quickly than before.

Botulinum neurotoxin A1, better known under the trademark Botox, is actually a nerve toxin produced by bacteria. It gained widespread public awareness through its use as a cosmetic aid. Many people have it injected into wrinkles to make them look younger.

The substance blocks signal transmission from nerves to muscles, thus relaxing them so that facial features appear smooth. What is less well known: Botox is also used very often in therapeutic medicine to treat conditions that can be traced back to cramping muscles or faulty nerve signals, including pains, spasms, bladder weakness, grinding of teeth, and misalignments, for example of the eyes. Botox is even used in treating stomach cancer, to block the vagus nerve and thus slow down tumor growth.

In a research project, a team led by Richard Kammerer of PSI's Laboratory for Biomolecular Research wanted to investigate whether it might be possible to influence the action of the toxin. "For that we have, together with biochemist Andreas Plückthun from the University of Zurich, produced 25 so-called DARPins," Kammerer says. DARPins are small, artificially produced proteins that work similarly to antibodies. They are used in therapy and diagnosis as well as in fundamental medical research.

The DARPins were expected to inhibit this function. But when the researchers also tested this DARPin in cell cultures, a completely opposite effect suddenly became apparent: The toxic action of the Botox took effect even more rapidly than usual.

Image source: Leka et al. (2023), Nature Communications.