Tendon Repair With Gene Therapy

Equine Science Update by: Mark Andrews, DVM

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