Innovative treatments against lower back pain in both dogs and humans

Marianna Tryfonidou is Professor of Regenerative Orthopaedics at the Faculty of Veterinary Medicine and researches back pain. She is currently busy developing two innovative treatments for dogs, which doctors will eventually also be able to use to treat people with back pain. ‘The strength of vets is that they have an eye for the similarities and differences between animal species.’

Drie dierenartsen doen lichamelijk onderzoek bij een hond op de behandeltafel.
Veterinarians thoroughly examine patients in the animal hospital, through physical, orthopedic and neurological examinations.

Many people do not know that back pain occurs in dogs too. Half of all dogs experience back pain’, says Tryfonidou. Back pain is also a major problem in people, she adds straightaway. ‘It is estimated that 80 per cent of the population experiences lower back pain or neck complaints at some time in their lives. At any given moment, we estimate that about 700 million people worldwide are suffering from such pain symptoms.’ 

Tryfonidou's work focuses on specific complaints that originate in an intervertebral disc. ‘Intervertebral discs are small cushions between the vertebrae and can - in both people and dogs - dry out and age’, she explains. ‘We estimate that 40 per cent of all back pain symptoms are caused by such deterioration in the intervertebral disc. For this group, there is no good treatment.’ The cause for the remaining 60 per cent of people with back complaints is found, for example, in osteoarthritis of the joints, muscle problems or a trapped nerve (hernia).
 

Een hond met lage rugpijn loopt over een drukplaat in de kliniek.
A patient with back pain walks over a pressure plate.
Dierenartsspecialisten meten hoeveel kracht de hond kan afzetten met zijn achterpoten terwijl hij over een drukplaat loopt.
On the pressure plate, motion analysis is performed in order to objectively measure the severity of symptoms.

Innovative medication release

One of the possible treatments that Tryfonidou is working on, focuses on patients, both dogs and people, with initial back complaints. For symptoms in the intervertebral discs, swallowing pain relief and anti-inflammatory medicines has little effect in general, explains the researcher. ‘Medicines that are administered via the stomach and intestines mainly end up in organs with a good blood supply. The intervertebral disc, however, has a poor blood supply and therefore medicines do not reach it or reach it in low concentrations.’

With a large team, Tryfonidou is therefore working on an innovative treatment. In this treatment, the medication is not administered via the blood but directly at the source of the pain in small spheres produced from biomaterials*. This packaging ensures that the medication remains in the intervertebral disc and is gradually released over a long period. ‘That has major advantages. We tackle the pain at its source, we only need a small dose, and we do not burden the rest of the body.’ Furthermore, we hope that in this way, the effect of the medicines will also persist for a long time.

*Biomaterials are synthetic or natural materials that are used for medical applications.

Limping less and happier 

The injections have already undergone various tests in the clinic. ‘We investigated dogs with back pain or osteoarthritis. Half of the group received an injection with the medication, and the other half received an injection without medication, a placebo. We are still busy analysing the data from the dogs with back pain, but for the dogs with osteoarthritis, we can already see that the treatment is effective. The dogs that receive medication limp less and have fewer inflammations in the joint. The owners also notice that they look happier and walk more easily.’ 

Tryfonidou is now trying to implement the treatment in the veterinary clinic. ‘We need to obtain approval from various bodies. We are investigating whether pharmaceutical companies are interested in producing the packaged medicine so that it ultimately ends up on the vet's shelf.'

Marianna Tryfonidou spuit een injectie met medicatie en biomaterialen in bij een hond die onder een ICT-scan ligt. Dit is om de exacte locatie te kunnen bepalen voor de injectie in de rug van de hond.
Tryfonidou injects medication and biomaterials under a CT-scan, in order to determine the precise location. The medication is released over an extended period of time, acting as anti-inflammatory and pain relief

15 million euros for cell therapy

Tryfonidou is also working on the treatment of advanced back complaints with a cause located in the intervertebral disc. ‘If the intervertebral disc is highly worn, then the medication will no longer be effective enough. For such cases, a stem cell therapy may be possible.’

To develop such a stem cell therapy, Tryfonidou has brought together a group of researchers from around the world. This iPSpine consortium received 15 million euros from the European Union. ‘Our idea is to insert advanced stem cells into the damaged intervertebral disc. We hope that these stem cells will then rejuvenate the intervertebral disc. Then somebody aged 60 years would acquire an intervertebral disc of somebody aged 40 years.’

However, that is easier said than done. ‘A damaged intervertebral disc is similar to a desert because it is so dried out,’ explains Tryfonidou. ‘Injecting stem cells without biomaterial would be like sending them into a desert with just a glass of water. They would not survive that. Therefore we also give the specialised stem cells a home made from biomaterials so that they can survive for longer.'

‘It's fantastic to have an impact on the treatment of both dogs and people with back pain’

Professor of Regenerative Orthopaedics at the Faculty of Veterinary Medicine

Expertise from around the world

The EU project has a duration of five years. ‘We will end with a study in which we will treat dogs from the clinic with the experimental stem cell therapy’, says Tryfonidou. For those experiments, the consortium contains a wide range of expertise. ‘We are working together with twenty partners from around the world. Their expertise ranges from cell biology to regeneration, and from biomaterials to ethics. Everybody plays an important role in developing the concept. Veterinary specialists from Utrecht University contribute a lot of knowledge about stem cells with a rejuvenating effect. In addition, we know a lot about the translation from laboratory to clinic.’

Strength of the vet

Tryfonidou is a passionate researcher who knows where her strengths lie. ‘What I find so fantastic about my work is that the treatments we develop can have an impact on both dogs and people. It's also great to coordinate and direct a consortium with so many different types of expertise. That is where my strength lies as both a vet and a researcher.’

‘What makes the training to become a vet so special is that, as students, we learn to look at the differences and similarities between a wide range of animal species. As vets, we also ask ourselves, for example: how do differences in tissues between animals lead to whether or not certain diseases occur? Due to the broad training and their affinity with (bio)medical research, vets can bridge the gap between the laboratory and the clinic.’

"It is an amazing opportunity to synergise all the expertise we have developed in our European labs"

Jerome Guicheux is Professor of Regenerative Medicine and works at the University Medical Centre of Nantes in France. ‘IPSpine consortium brings together the most eminent labs working on intervertebral disc degeneration in Europe and Asia. It is an amazing opportunity to synergise all the expertise we have developed in our European labs. Without the support of the European Research Council, it would have been impossible to set-up such a large, risky and ambitious project.’
‘IPSpine consortium will make it possible to transfer notochordal cells generated from induced pluripotent stem cells to veterinary clinics. That is really exciting because, at present, no therapeutic solution exists for either animal or human patients suffering from lower back pain. We are highly committed to transferring innovative therapies to animal clinics. The concept "One Health" (also named "Manimal" in France) allows us to welcome several veterinary surgeons in my lab. Together with our human clinicians, they are developing some therapeutic concepts for both animal and human patients. Gathering both these types of expertise will allow the basic concept to be rapidly transferred the clinics.’

“It is tremendous that we can work with other scientists, engineers, clinicians, social scientists and commercial partners to really tackle the entire problem."

Keita Ito is Professor of Orthopaedic biomechanics at Eindhoven University of Technology and is collaborating in the iPSpine consortium. ‘The consortium is a broad mix of experts from a variety of disciplines. It is tremendous that we can work with other scientists, engineers, clinicians, social scientists and commercial partners to really tackle the entire problem. Together we hope to quickly develop a treatment by taking advantage of different technologies and combining the individual advantages of these synergistically. We tend to focus on human medical problems, but other species often suffer from the same medical complaints too. We can learn from the similarities and differences between species and well as from similar diseases, and we can learn from how each of these different patient groups responds to the treatments we develop. Therefore, by working with both veterinary and human clinicians, we can advance our solutions safer and faster.’
 

"The basic structures are the same in all animals, but due to the arrogance of Homo sapiens, human medicine has unfortunately created a large and artificial distance between itself and veterinary medicine."

Cumhur Öner, Professor of Spinal Surgery at UMC Utrecht. ‘One Health gives us a fantastic opportunity to bridge the gap between human medicine and veterinary medicine. The basic structures are the same in all animals, but due to the arrogance of Homo sapiens, human medicine has unfortunately created a large and artificial distance between itself and veterinary medicine. However, the similarities and differences can act as a large source of knowledge. Together with the Faculty of Veterinary Medicine, we are working on frequently occurring problems caused by the degeneration of the intervertebral disc in both people as well as some other animal species. This work will enable us to better understand the parallels and differences between the species, and we can utilise the experiences of non-human patients as part of the translational research.’
 

This article was publisched in Vetscience International, January 2020.

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