Tendon repair with gene therapy

Gene therapy techniques have been used to help cure horses with tendon and ligament injuries, a study involving experts at the University of Nottingham has shown.

This work, leading on from their work published last year, has been carried out as part of a collaborative research project between academics in the University's School of Veterinary Medicine and Science and Kazan Federal University and Moscow State Academy.

The big problem with tendon injuries is that they repair leaving scar tissue, which is less elastic than the normal collagen found in healthy tendons. This leaves them prone to further damage.

By injecting plasmid DNA into the torn ligaments and tendons the researchers were able to see that blood vessels developed within the tissue and the tissue grew back without leaving scar tissue behind.

Dr Catrin Rutland, Associate Professor of Anatomy and Developmental Genetics at The University of Nottingham, said: “This innovative work is truly exciting, not just for veterinary medicine but also in human medicine. Seeing the quick recovery period, the pain relief to the injured animals and watching the blood vessels develop to help the tissue repair was amazing. It gave us real insights into how and why these techniques work.”

Professor Albert Rizvanov, Kazan Federal University who led the study, said “The treatments available at the moment often do not work, or result in relapse in 60 per cent of the cases or take many months to work.”

“This treatment could potentially be used in not only for horses but other animals and humans with ligament and tendon injuries.”

He pointed out the importance of using genes derived from horses to produce the plasmid DNA: “It is essential that we used horse genes to create this gene therapy treatment. By using species-specific genes, we ensured that proteins which are being synthesized are natural for the horse and won’t cause any unwanted immune reactions.”

Veterinary Surgeon Dr Milomir Kovac, said “The horses used in our study had gone lame naturally but with the treatment most of them were back to their previous levels of movement and fitness within a very short time period and were no longer in pain. In addition, we did not see the high levels of lameness reoccurring in our patients.”

 “Our gene therapy worked within just a few weeks. Therefore, it has a high rate of healing, a low chance of relapse and works quickly – a significant medical discovery.”

The team of scientists and clinicians inserted equine genes for Vascular Endothelial Growth Factor (VEGF164) and Fibroblast Growth Factor 2 (FGF2) into a single plasmid DNA. Once they had injected it inside the injured ligament or tendon, natural horse proteins were produced which helped blood vessels to grow thus promoting healing.

Seven horses with naturally occurring injuries of the superficial digital flexor tendon (SDFT) (tendinitis) and in three horses with suspensory ligament branch desmitis were included in the study.

To assess the response, the research team measured the total cross-sectional area of the affected tendon or ligament, the percentage cross sectional area of the lesion, the echogenicity score, and the percentage of parallel collagen fibres.

They observed a rapid regeneration of both the SDFT and the suspensory ligament in most horses within 2–6 months of treatment. They report that ultrasonographic characteristics of lesions started to improve notably at 3 weeks.

They found that the direct gene therapy resulted in an earlier reduction of the degree of lameness in 9 out of 10 horses.

The research was funded through a Program of Competitive Growth at Kazan Federal University. The next step for the team is to find funding which will enable them to further develop the treatment and ultimately get it out into clinics and veterinary surgeries.

For more details, see:

Gene Therapy Using Plasmid DNA Encoding VEGF164 and FGF2 Genes: A Novel Treatment of Naturally Occurring Tendinitis and Desmitis in Horses.

Frontiers in Pharmacology (2018)

https://www.frontiersin.org/articles/10.3389/fphar.2018.00978/full

New Equine Virus test available

A recently discovered virus, which can lead to severe neurological disease and may prove fatal, can now be identified using a new diagnostic test developed by Portugese biotech company Equigerminal.

New Equine Virus (NEV) was first identified in 2013 by Portuguese scientist Isabel Fidalgo-Carvalho, during the course of her PhD studies at the Universities of Oporto and Pittsburg.

She noticed unusual anaemia and severe neurological signs in horses, which initially she attributed to Equine Infectious Anaemia (EIA or “swamp fever.”)

Affected horses cross-reacted with EIA virus but gave negative results in the official (“Coggins”) test. Subsequent research found that the horses were actually suffering from a different disease.

The virus could be isolated from blood and cerebrospinal fluid of sick horses. It was identified as a lentivirus (the family of viruses that include human immunodeficiency virus (HIV), as well as EIAV) and was given the name “New Equine Virus” (NEV).

NEV has been shown to cause anaemia and respiratory and neurological signs. Sometimes it can prove fatal.

Fidalgo-Carvalho points out “We believe that NEV has been undetected for so long because previously signs were being attributed to other diseases – such as swamp fever or herpes virus”

Once the horse has been tested the appropriate treatment can be given and the spread of the disease prevented. Treatment is currently targeted towards improving the general well-being of the horse, health monitoring, and boosting the animal’s immune system.

Having developed the test, their aim now is to study the NEV seroprevalence worldwide and to explore the association of NEV with equine viral encephalitis.

The next stage is to find a treatment and hopefully, a cure for NEV.

For more details, see:

http://equigerminal.org/index.php/2018/06/20/new-equine-virus-nev-indiegogo-campaign/

http://equigerminal.org/index.php/2018/08/15/oral-presentation-11th-international-congress-for-veterinary-virology/

Increased Atypical Myopathy risk

Bare pastures and potential hay shortages, coupled with early transatlantic storms blowing seeds from laden sycamore trees, have created the ‘perfect storm’ to increase the risks of atypical myopathy for grazing horses, warns the British Equine Veterinary Association (BEVA). Experts are advising horse owners to take steps now to minimise the risks of this fatal disease.

Atypical myopathy, as a sudden onset of muscle disease has been recognised in horses for over 60 years but its cause, the toxin hypoglyxin A, was not identified until 2013. In the UK, the most common source of the toxin is now known to be the Sycamore tree (Acer pseudoplatanus), a member of the maple tree family. The Box Elder (Acer negundo) is the most common tree to cause the disease in North America. Both trees share the typical helicopter shaped fruit that help to distribute their seeds over long distances, typically several hundred metres, but reportedly up to 4km. The high winds we are experiencing early this autumn can result in greater spread of seeds for the simple reason that they have yet to fall naturally and the high winds will bring down large numbers of seeds over a short duration of time.

“Horses do not typically choose to eat sycamore seeds, however when pastures are bare, there is a greater tendency for them to be ingested as horses are foraging for every last blade of grass,” explains BEVA member Adam Redpath, a member of the team of equine medicine experts working at Nottingham Vet School, who is particularly concerned about the combined disease threats that present this year.

A range of factors affect the amount of toxin in sycamore seeds, meaning the 'toxic dose' can vary from less than 100 to several thousand single seeds. Given that each tree can shed over 20,000 fruit, each with two seeds, the amount on pasture can be considerable. In the spring, seedlings represent a risk to horses and can affect hay made from contaminated pasture. Seedlings at the edge of watercourses can also contaminate water supplies, especially when trampled as horses walk across them.

BEVA is urging horse owners to take early steps to prevent the disease by limiting access to sycamore seeds:

·         Identify trees both around grazed fields and nearby. Trees are often easiest to identify in the summer when in full leaf, rather than in the autumn, when leaves have largely fallen. The characteristic maple leaf shape is easy to spot, although if in doubt a test is available from the Royal Veterinary College as a result of work funded by The Horse Trust.

·         Collect seeds or exclude horses from affected areas using electric fencing or stabling.

·         Feed supplementary hay to try and prevent horses from excessive foraging for short blades of grass and inadvertent ingestion of seeds. But ensure that hay does not become contaminated by seeds.

·         Don’t rashly fell trees when laden with seeds as this can cause a sudden and massive contamination of the pasture. Consider local regulations, tree protection orders and tree ownership if felling is the only option.

·         Monitor horses carefully even after they have been moved from affected pasture as disease can occur up to four days after exposure.

The clinical signs of atypical myopathy vary considerably. Most consistent is the passing of dark brown urine (myoglobinuria) due to muscle breakdown. Horses usually become weak and reluctant to move and may lay down, but usually have a normal or increased appetite. In the most severe case the horse will develop very severe colic-like signs as a result of significant pain. In some horses the severity of muscle pain leads to euthanasia on welfare grounds. These signs occur because the active toxin which prevents muscles from undergoing normal energy metabolism. It can affect all muscles in the body including the respiratory muscles and heart.

“Early veterinary intervention is essential to achieve a favourable outcome,” explains Adam. You should contact your vet immediately if you spot any of the signs. Check your fields for sycamore seeds as this will help your vet to make a rapid diagnosis. Specific blood tests have been developed to both measure exposure to the toxin and to make a diagnosis, thanks to research funding from The Horse Trust.”

Hay-fed horses may lack nutrients

Research has shown that horses on a hay-only diet may not digest some nutrients as effectively as those fed combination diets and could benefit from dietary supplementation.

With winter approaching and grass growth stunted by the UK’s arid summer many horse owners are feeding hay or haylage earlier than usual. But simply giving horses hay may not be enough for optimum health, even if it meets their energy needs and requirement to chew.

The study, carried out by WALTHAM® Equine Studies Group, who provide the science underpinning the SPILLERS® brand, in collaboration with Michigan State University, discovered that feeding a hay-only diet resulted in reduced digestibility of many macro and micro minerals (such as calcium, magnesium, copper and zinc).

The study involved a group of healthy adult horses and a group of healthy aged horses being randomly assigned on a rotational basis to one of three diets that supplied similar gross energy over a five-week period: hay, hay plus a starch and a sugar rich concentrate or hay plus an oil and fibre rich concentrate. The micro and macro nutrient digestibility was determined for each diet.

An analysis of faecal and urine samples showed that while the horse’s ability to digest key nutrients does not appear to decrease with age across any of the three diets fed, the hay diet was lower than the other two diets for fat intake, amount digested and percent of apparent digestibility. However, perhaps most importantly the apparent digestibility for various macro and micro minerals (including key trace elements) was consistently lower when fed the hay diet compared with the other two diets.

Clare Barfoot RNutr, the research and development manager at SPILLERS® said: “It seems that many micro and macro minerals are less available to the horse from a hay only diet than when the hay is fed together with a fortified feed. This strongly suggests that horses and ponies fed hay only diets may require additional supplementation such as a balancer to maintain good health and well-being.”

For more details, see:

Comparison of nutrient digestibility between three diets for aged and adult horses.

Sarah Elzinga, Brian D. Nielsen, Harold C. Schott, Julie Rapson, Cara I. Robison, Jill McCutcheon, Ray Geor and Patricia A. Harris.

Journal of Equine Veterinary Science (2017) vol 52 p89

https://doi.org/10.1016/j.jevs.2017.03.126

Approaches to farrier care and laminitis prevention

Farriers need to work closely with horse owners to spot the subtle signs of the painful condition laminitis, a new study in Equine Veterinary Journal reports.

During this unique study researchers from the University of Surrey’s School of Psychology and School of Veterinary Medicine conducted in-depth interviews with farriers and horse owners to understand how their relationship and their approach to equine care can help prevent laminitis. 

Laminitis is a painful, potentially disabling and fatal disease that affects horses’ hooves. It can lead to a horse being humanely euthanised if the effects become so serious that it is inhumane to continue treatment.

Analysis of the interview data revealed two approaches to farrier care: either task-focussed or holistic care-focussed.

Researchers found that farriers who have a holistic approach, place an emphasis on building long-standing, trusting relationships with owners. It is this approach and a commitment to the overall health of the horse that can potentially reduce instances of laminitis.

The study also found that farriers who are more technically-focused, can work well with owners who have knowledge and understanding of laminitis, but are not providing more welfare-focused support, particularly useful for owners new to caring for horses.

Figures reveal that 75 per cent of horses in Great Britain are cared for by their owner, many of whom are new to horse ownership and may not have the knowledge or skill needed to care for horses at risk of laminitis.  In such instances, the role of the farrier is invaluable in helping to identify potential problems such as obesity, so that appropriate referrals can be made to equine vets, nutritionists and other equine professionals.

Lead author of the paper, Jenny Lynden from the University of Surrey, said: “The relationship between a horse owner and their farrier is not to be underestimated.  When more holistic support is required by an owner, farriers who want to and have trained to engage in this way, have a huge role to play in providing this support.  The key is to ensure that farriers and owners can be ‘matched’ appropriately, so that owners who require more holistic-focused interventions can access farriers who can and want to offer this type of support.”

A new survey is seeking to extend this understanding by finding out how horse owners and farriers prefer to work with each other. This will help inform support for farriers’ continuing professional development.

If you are a horse owner, please complete this survey:

http://surveys.fahs.surrey.ac.uk/Equine_Survey/

If you are a farrier, please complete this survey:

http://surveys.fahs.surrey.ac.uk/Farrier_Survey/

For more details, see:

Contracting for care – the construction of the farrier role in supporting horse owners to prevent laminitis

J. Lynden J. Ogden T. Hollands

Equine Vet J. (2018); vol 50, pp658-666. 

https://doi.org/10.1111/evj.12950

Equine Behaviour Forum Scientific Seminar 2018

The Equine Behaviour Forum (EBF) has announced a change to the programme of their upcoming scientific seminar.

Jenni Nellist BSc(Hons) MSc, (ABTC) (APBC) will join Rachel Bedingfield and Dr Andrew Hemmings in presenting reports on research into equine behaviour. She will be discussing how human effects on the horse's physical and social environment affect mood and behaviour. Her talk will focus on sports horses and feral ponies; on the hill and in closer confinement; from management and husbandry to training.

The seminar will be held at Myerscough College, Lancashire on Saturday 29th from 10.30 am – 4.30 pm.

Everyone is welcome including non-members, at a cost of £15 per person (members) and £35 (non-members). Students £5.00.

Contact: Judith Turner, Tel: (01423) 770144, email: equiphile@talktalk.net

Or look at the EBF facebook page [11April]:

https://www.facebook.com/groups/970610492997325/