Tetanus toxin is a highly potent neurotoxin that can lead to fatal cramps. A new study shows that it could possibly help paralyzed people in the future to stop and reverse muscle wasting in immobile parts of the body. In paraplegic dogs, injections of the poison into the affected muscle areas caused the muscle mass to increase again. The ability to walk did not improve in the four-legged friends. Still, the researchers are confident that further studies could lead to clinical application in humans.
If the bacterium Clostridium tetani enters the body through a wound, it produces what is known as tetanus toxin. It is a powerful neurotoxin that causes muscle spasms throughout the body. This so-called tetanus is fatal in many cases. As early as 1946, however, the Moldovan neurologist Boris Sharapov put forward the thesis that the tetanus toxin could be used therapeutically against paralysis. During the Second World War he had observed that people who were paralyzed from gunshot wounds and who happened to contract tetanus were able to move their paralyzed limbs actively again. He suspected that the poison had positively stimulated the preserved nerve cells.
Paralyzed dogs as participants
A team led by Anna Kutschenko from the University of Göttingen has now continued this approach. “So far, the treatment options for patients who are paralyzed due to spinal cord injuries are very limited,” the researchers write. “That is why we tested a novel pharmacological approach in which motor neurons in the spinal cord are reactivated by targeted injections of low-dose tetanus toxin.” The researchers were inspired by Sharapov’s observation. “Today we know that tetanus toxin, when we inject it into the muscle, switches off inhibitory nerve cells at the spinal cord level,” explains Kutschenko. “This reactivates motor nerve cells that directly target the affected muscles.”
For their study, the researchers recruited 25 dogs of different breeds through advertisements in magazines for dog owners, all of whom were paraplegic due to a herniated disc. The dogs were divided into two groups, one group being injected with low-dose tetanus toxin into the paralyzed muscles and the other group receiving a placebo. In order to avoid distortions caused by certain expectations, neither the researchers nor the owners knew which dogs had received the active ingredient and which had received a dummy drug.
Thicker muscles thanks to tetanus toxin
Before the injection and four weeks afterwards, the researchers measured the muscle thickness in the affected limbs using ultrasound and also recorded via video to what extent the dogs were able to stand and move. In addition, they asked the owners whether their respective protégé behaved abnormally after the treatment, had side effects and to what extent he was able to hold urine and feces – which is a problem for many paraplegic dogs.
The result: “Four weeks after the injection of tetanus toxin into the muscles affected by muscle wasting, the new measurement showed a significant increase in muscle thickness compared to the dogs injected with placebo,” reports Kutschenko’s colleague Anja Manig. Some owners of treated dogs also reported that their four-legged friend had better control of their bladder and bowels again. With regard to the ability to move on one’s own, however, there was no consistent picture. In both the treated group and the placebo group, there were some dogs who got better walking abilities and others who got worse.
Does combination with physiotherapy make sense?
“This is in contrast to a preliminary examination that we carried out with four dogs,” write the researchers. In these four dogs, the ability to walk had improved significantly in the weeks following the injection. “An important difference to our preliminary study was that the dogs also received regular physiotherapy, which was not the case in the current study,” said the researchers. “We may have underestimated the influence of this factor and accompanying physiotherapy is crucial in order to benefit from the positive effects of the tetanus toxin.”
In future studies, the researchers want to explore to what extent the tetanus toxin can also help people who are paralyzed due to spinal cord injuries, strokes or multiple sclerosis. Among other things, it is about finding a safe dosage. In this context, it could play a role that most people were immunized against the poison through the tetanus vaccination. However, previous studies in mice suggest that this has little effect on local efficacy. From the point of view of the researchers, their results could in the future help to counteract muscle wasting in paralyzed people, avoid the resulting secondary diseases and possibly even give people back some of their mobility.
Source: Anna Kutschenko (University of Göttingen) et al., Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002 / jcsm.12836