Rejuvenation treatment for worn out intervertebral discs

Millions of people and animals could benefit from a treatment for back pain. Marianna Tryfonidou, professor of Regenerative Orthopedics at Utrecht University's Faculty of Veterinary Medicine, has been awarded a 1.5 million Euro Vici grant by the Dutch Research Council (NWO) to investigate the potential of a nano rejuvenation treatment for worn out intervertebral discs.

Over 200 million people worldwide suffer from lower back pain due to worn out intervertebral discs. These cushions between the vertebrae are then dried out - usually due to ageing, a mix of hereditary causes and (too) many taxing activities for the back. No suitable treatment exists for this type of back pain - which can have a huge impact on daily life - yet.

Dogs also suffer from back pain and sometimes have to be euthanized for this reason. Earlier research by Marianna Tryfonidou and colleagues showed that the solution for this may lie in incredibly powerful cells: the notochord cells. These play an important role in the formation of the embryo. The notochordal cells persist in the intervertebral discs and disappear during childhood. 

In certain breeds of dog - for example the Labrador retriever, Dobermann pincher and Golden retriever - the notochordal cells do not disappear, but remain active in the intervertebral discs well into adulthood. It is striking that possible back problems in these dogs only develop at a later age.

Potential for rejuvenation

"There is a link between the disappearance of these special cells and the onset of wear and tear on the intervertebral discs," explains Tryfonidou. "By comparing dogs and humans, we discovered that these cells have great potential for regeneration or rejuvenation of the intervertebral discs. A cool discovery." Tryfonidou now wants to use these rejuvenating properties to refurbish worn out intervertebral disc and thus reduce back pain. 

Her first goal is to find out exactly how the rejuvenating properties of notochord cells work. "We already know that notochord cells transmit their rejuvenating messages to other cells with the help of released vesicles. These vesicles safely store the messages, for example proteins and RNA," says Tryfonidou. "We want to know which of those messages are the most important."

Subsequently, she wants to select the most rejuvenating messages and package them in a vesicle made in the lab: a kind of microsphere made of fat. The researchers then want to inject these microspheres into the worn out intervertebral discs. 

"We tackle the pain at its origin"

Small dose, big effect

Because the researchers inject the microspheres into the intervertebral disc, the medication is immediately in the right location. This has major advantages. "We tackle the pain at its origin, we only need a small dose and we do not burden the rest of the body." They hope the effect of the medication to last for at least a year.

The biggest challenge will be to choose the right rejuvenating messages from the many hundreds that Mother Nature has to offer, says Tryfonidou. "In nature, there is no single message to get something done. There are always many helpers. That is why we have to compare hundreds of messages to choose the best ones. But luckily, we are not starting from scratch. We already know that two candidates will have a significant rejuvenating effect. They will end up in the microspheres anyway, and we will build the rest of the messages around them."

If this strategy is successful, the scientists can also apply the principle behind the microspheres to other problems. By choosing different messages and packing them into a microsphere, they can for example try to counteract inflammation or tissue breakdown, or reduce pain. "With advanced wear and tear, a rejuvenation treatment no longer helps. Additional action is then needed."

Ultimate dream

"I already suffered from back pain as a young girl. I learned that the way you live, sit and use your back has a big effect on the symptoms. Our dream treatment is therefore not intended to replace a healthy lifestyle, but rather to complement it. My ultimate dream is to develop a treatment for back pain that works for both dogs and humans. That is a great example of One Medicine: the principle that people can benefit from research, diagnostics and treatment methods from the veterinary world and vice versa. Usually, veterinary medicine benefits from human medicine. Now we can give something back. I think it's really cool that as a veterinarian, I can make a difference for animals and people."