Gene therapy techniques have been successfully employed in a British study to help cure horses of lameness in what is being described as a significant medical discovery.
The techniques were said to have worked within weeks, with a low chance of relapse.
The researchers, who injected plasmid DNA into torn ligaments and tendons, were able to see that blood vessels developed within the tissue and the tissue grew back without leaving scar tissue behind. This is essential as it helps the horse to walk, trot and gallop again.
The findings of the research have been published in the journal Frontiers in Pharmacology.
The work was carried out as part of a collaborative research project between academics in the University of Nottingham’s School of Veterinary Medicine and Science and Kazan Federal University and Moscow State Academy.
This larger study compliments their work published last year and provides more evidence that these techniques could be used to help horses who have gone lame due to tendon or ligament injury.
“This innovative work is truly exciting, not just for veterinary medicine but also in human medicine,” says Dr Catrin Rutland, associate professor of anatomy and developmental genetics at the University of Nottingham.
“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, of Kazan Federal University, who led the study, says lameness affects not only the ability to walk but also causes pain.
“This treatment could potentially be used not only for horses but other animals and humans with ligament and tendon injuries.
“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.
“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 the 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. The most promising treatments emerging have a 20 per cent relapse rate but also take 5-6 months to work.
“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 had previously reported on two horses who had received cutting-edge treatment, but this larger pioneering study helped to show the results achievable in superficial digital flexor tendons and the suspensory ligament branches. Damage to these two areas can cause chronic and debilitating lameness.
The research centered on seven horses with naturally occurring injuries to their superficial digital flexor tendon (tendonitis) and three horses with suspensory ligament branch desmitis.
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 ligaments or tendons of the horses, natural horse proteins were produced which helped blood vessels to grow, thus promoting healing. This then ensured that the tissue can grow where necessary to heal the broken tendon or ligament.
The team was also able to identify how the genes repair the tissue and the underlying mechanisms.
Professor Rizvanov said the priority was getting horses fit and active again.
“With this progressive treatment we can advance medicine in not only tendon and ligament repair but also in other injuries, disorders – and in humans.”
And the outcomes for the 10 horses? Eight of the horses returned to their pre-injury level of performance by two to six months after the completion of treatment.
The ninth horse, who had presented with severe suspensory ligament branch desmopathy, showed no significant ultrasonographic improvements in the first two months after treatment. However, it improved clinically and became less lame.
The final horse, who had presented with severe tendonitis of the superficial digital flexor tendon, returned to its pre-injury level of performance, but experienced re-injury six months after treatment.
“This data is highly promising,” the study team wrote in their paper.
“However, further research in experimental models, with the histopathological, immunohistochemical and gene expression evaluation of the equine tendon/ligament after gene therapy application is required in order to fully understand the mechanisms of action.
“This treatment and the significant clinical impacts observed represents an important advancement in the field of medicine.”
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 the researchers to further develop the treatment to get it into clinics and veterinary surgeries.
Gene Therapy Using Plasmid DNA Encoding VEGF164 and FGF2 Genes: A Novel Treatment of Naturally Occurring Tendinitis and Desmitis in Horses
Milomir Kovac, Yaroslav Litvin, Ruslan O. Aliev, Elena Zakirova, Catrin S. Rutland, Andrey Kiyasov and Albert A. Rizvanov.
Frontiers in Pharmacology https://www.frontiersin.org/articles/10.3389/fphar.2018.00978/full
The study is published under a Creative Commons License.