Translational medicine bringing a new cure for arthritis


Translational medicine is collaborative science that translates work in the laboratory into practical medical treatments – it is sometimes termed ‘bench to bedside medicine’. Because it often includes trials on animals it can be controversial.  So can animal testing be justified?

Scarlett MccGwire put on her wellies and met up with Francis Henson to find out.

Dr Frances Henson:  I’m Frances Henson, Research Fellow in the Division of Trauma and Orthopaedic Surgery, Department of Surgery, Addensbrooke’s Hospital, Cambridge, and I am also Senior Lecturer in Equine Surgery, Department of Veterinary Medicine, Cambridge Veterinary School.

What I do is work in the lab with basic scientists to generate treatments for various orthopedic diseases.  I am interested in lame animals and lame people and we use a large animal model – a sheep – to try our experiments before we take them on to use them either to treat human patients or veterinary, animal, patients.

Our current research is looking at a novel bio-material.  I have colleagues in Newcastle who have made a brand new bio material, they have put two special materials together and they are going to be using those to treat large surface defects in joints – knee joints in people – that will also be applicable to our veterinary species.

Scarlett MccGwire:  You are trialing this on sheep?

FH:  Yes, we are.  What we do with these osteochondral plugs, as we call them, is we take our sheep, make little holes in the joints and we fill those holes with our novel treatmentt to prove that treatment is both safe and really offers a significant improvement in the expected outcome.  If you didn’t put the scaffold in, the joints wouldn’t heal.

SM: What are you finding out so far?

FH: We are finding that these new products are very good at treating joint surface defects.  Within our group, we have developed a novel way of looking at this.  We don’t want these animals to suffer pain, so we monitor their pain, immediately after surgery and through the experiment because we do data analysis, recording the amount of weight bearing on the leg that has been operated on.  Interestingly we can show no difference in the animals we have operated on, compared to animals that have not been operated on, very quickly – within a matter of hours after the surgery.  The surgical procedures are very benign and the osteochondral plugs really allow the joints to heal very well.

SM: What does this mean for humans?  Will knee replacement surgery be much easier?  Is this the end of the pain of arthritis?

FH: Let’s take these in two parts.  First, the early osteoarthritis.  Arthritis occurs when you have a defect in the joint, the joint is very ppor at healing itself and at the current time, if we have pain in our joint, the doctor give us painkillers and we limp around for a while until it is too painful and you go for a joint replacement (which is not a cure, it is amputation and putting in a prosthesis.

The joint surface defects we want to cure with the scaffold are big lesions in joint, due to sports injuries and trauma in road traffic accidents. These cause big damage in the joint and currently there is no treatment for that.  Left untreated it will go to arthritis.  We have the ambitious hope that using these scaffolds we can stop osteoarthritis before it starts, cure the joint and get it back to a healthy environment.

SM: We are using sheep to make incredible progress for humans?

FH: We are using our sheep to make incredible progress, I hope, in curing joint disease in both humans and animals.  I am a veterinary surgeon, I spend half my time in the lab, but the other half in my surgery with animals, particularly horses and the treatments we are developing are all part of a ‘one health’ agenda. If we can treat joint defects in man, we can also treat them in animals.  So, while the sheep is being used, it is for the benefit of animals in veterinary medicine and in human medicine.

SM: So we are talking about horses, pets – animals we spend a lot of money on.

FH: Yes, that’s right.  Horses, dogs and pet small animals, pet pigs, small breeds of sheep.   There is no reason a sheep couldn’t benefit directly from this treatment, I suppose it depends on economics, how much it would cost, how much an owner is prepared to pay.  But the treatment is as available for sheep as for any other animal.

SM:  A lot of people think that research on animals is cruel.  You are a vet.  You are in the business of curing animals, not causing them pain.  How do you justify it?

FH: I justify it because I want animal orthopedic treatments to have a step change improvement.  We want to cure osteoarthritis.  You can do a hip or knee replacement for himans but for a horse with a similar condition, it is a dead horse.  Or sheep – it is a dead sheep. We don’t have any kind of joint replacement.  Si it comes back to whether we feel comfortable with the idea that an individual sheep contributes to amassing this data.  In terms of the effect on the sheep, we do the surgical procedures very carefully and they are certainly less invasive than getting a dog or cat spayed (that’s major intra-abdominal surgery). Whereas our sheep have very small wounds in their knees and they recover within minutes of the surgery.

SM:  The great problem, though, with animal experiments is that the animals are killed at the end.

FH: That is correct, but with our experiments, and this is important, the sheep that we use have already been ‘saved’ from the abattoir.  We use sheep that are known as ‘cull ewes’.  They have been used for breeding, but have been sent by farmers to market because they can no longer get in lamb.  These are adult female sheep.  We take them out of the abattoir food chain and on average they get at least an extra 9-12 months of individual care during which time they put on a significant amount of weight.  Yes, we do have to lose them at the end of the experiments but they don’t suffer – that, to me, would be the stressful situation of group transport, being taken to the abattoir  – no, we let them go in peaceful surroundings, and treat them with a great deal of individual respect.

Translational medicine is vital from a biological and a regulatory standpoint. Biologically it is difficult to make assumptions that a treatment will work in an animal or human joint, just by looking at it in the test tube in the lab.  Rats and mice are very different from large animals and human models, so you can’t extrapolate from the lab and the small animals into horses, sheep or people.  You have to trial it whether you like it or not.

And for regulation, if we want a new product to be licensed, EU and US law says it has to be tested in a large animal model.  The current regulatory framework is that this work has to be done.

SM: Give me some examples of translational medicine which has made a real difference to humans and animals.

FH: For humans, the clearest example is heart transplants.  A lot of the background work was done in pigs.  Heart/lung transplants are almost standard now, and we perhaps forget their origins.

And one of the very interesting treatments to benefit humans and animals is stem cell therapy.  Stem cells have the capacity to regnerate any body tissues and a lot of these therapies have been trialed in animal models eg in brain diseases.  This will be a huge area of growth in the future.

Photo:  Mrs Sheep by Katie Dalton


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