Inactivated tetanus as an immunological smokescreen; a major step
towards harnessing tetanus-based therapeutics.
Background and Purpose: Tetanus neurotoxin has many potential
therapeutic applications, due to its ability to increase localised
muscle tone when injected directly into a muscle. It is a closely
related molecule to botulinum neurotoxin (most commonly known as Botox),
which has been widely used to release muscle tension for therapeutic and
cosmetic applications. However, tetanus toxin has been relegated to the
“maybe pile” for protein therapeutics — as most of the population is
vaccinated, leading to highly effective antibody-mediated protection
against the toxin. The potential for tetanus-based therapeutics remains
substantial if the problem of pre-existing immunity can be resolved.
Experimental Approach: A well-established murine model of localised
muscular contraction was utilised. We administered functional tetanus
toxin combined with an immunogenic, but functionally inactive, decoy
molecule. Key Results: Incorporation of the decoy molecule greatly
reduces the dose of active toxin required to induce a localised increase
in muscle tone in mice vaccinated with the human toxoid vaccine.
Conclusion and Implications: Our results clearly demonstrate that the
barriers to developing a tetanus toxin therapeutic are not
insurmountable and the technology presented here is the first major step
towards realising the therapeutic potential of this powerful neurotoxin.
Opening the therapeutic potential of tetanus toxin will have huge
implication for the wide range of diseases caused by low-tone muscle.