Wednesday, October 18, 2017

Research: Direct-Injection Gene Therapy Proven Successful for Soft Tissue Lameness Injuries in Horses

Two dressage horses recovered from suspensory ligament and superficial flexor tendon injuries following direct injection of enhanced equine DNA into the injury site. The research was published this week. (Photo: Catrin Rutland, Assistant Professor of Anatomy and Developmental Genetics, University of Nottingham School of Veterinary Medicine)

Can we use gene therapy to repair injuries? Specifically: Can genetic material (DNA) be injected directly into a soft tissue injury site and repair damaged tissue that is causing a performance or race horse to be lame?

An international group of British and Russian researchers believes that not only can it be done--they’ve done it. Twice. In a ground-breaking pair of case studies, Professor Albert Rizvanov (Kazan Federal University, Russia) and his group confirm that by injecting pure DNA into an injured horses' suspensory ligaments and superficial digital flexor tendons, they were able to completely restore the function in these vital areas.

The authors also stated that the horses presented at the clinic with naturally occurring injuries; the genetic treatment conformed with US Food and Drug Administration and EU standards. Similar treatments had been used experimentally in dogs and humans in tests by some of the team members.

The first case study was conducted on a successful 13-year-old dressage horse. The horse's clinical diagnosis was Grade 2 desmitis of the lateral branch of the suspensory ligament. A second treatment benefited a 9-year-old half-bred Trakehner, also used for dressage; he had been diagnosed with Grade 3 tendinitis of the superficial digital flexor tendon.

"We showed that gene therapy used within a period of 2–3 months after the injury resulted in the complete recovery of functions and full restoration of the severely damaged suspensory ligament and superficial digital flexor tendon," the authors state in the article.

The research also showed that the tissue within the limbs had fully recovered and that 12 months after the revolutionary treatment, the horses were completely fit, active and pain free.

No side effects or adverse reactions were seen in the horses.

The main advantage of gene therapy used in this study was the application of a combination of the pro-angiogenic growth factor gene VEGF164, enhancing growth of blood vessels, and bone morphogenetic protein 2 (BMP2), which plays an important role in the development of bone and cartilage.

To avoid undesirable immune reactions, both genes were derived from horses, thus resulting in biosynthesis of natural horse proteins in treated animals. Both recombinant genes were cloned into single plasmid DNA which is commonly regarded as non-immunogenic and a biologically safe gene therapy vector.

Since these injuries may affect not only horses but many other animals and humans, the study carries potential implications for the future direction of human and veterinary medicine, potentially with fewer relapses and shorter recovery times. Much more work will be needed to investigate safety and efficacy. A larger clinical trial has been started.

Professor Rizvanov formed a collaboration with scientists and clinicians within his laboratories at Kazan Federal University, Kazan, Russia and also with Moscow State Academy of Veterinary Medicine and Biotechnology, Russia and the School of Veterinary Medicine and Science, University of Nottingham, United Kingdom. Working together to heal ligament and tendon injuries has been the primary goal of the work.

Their work has now been published in the international journal Frontiers in Veterinary Science and is titled “Gene Therapy Using Plasmid DNA Encoding Vascular Endothelial Growth Factor 164 and Fibroblast Growth Factor 2 Genes for the Treatment of Horse Tendinitis and Desmitis: Case Reports.”

To read the full article please go to:

Full citation:
Kovac Milomir, Litvin Yaroslav A., Aliev Ruslan O., Zakirova Elena Yu, Rutland Catrin S., Kiyasov Andrey P., Rizvanov Albert A. (2017) Gene Therapy Using Plasmid DNA Encoding Vascular Endothelial Growth Factor 164 and Fibroblast Growth Factor 2 Genes for the Treatment of Horse Tendinitis and Desmitis: Case Reports. Frontiers in Veterinary Science. 4. DOI=10.3389/fvets.2017.00168.

For more information, contact Professor Albert Rizvanov:

Dr. Rutland's imaging work was displayed on the cover of the September 2017 edition of HoofSearch. She assisted with the preparation of this article.

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