Gene therapy: Second stage of research documents further success for rehabilitation of tendon injuries in lame horses

Equine surgeon Milomir Kovac performs an ultrasound on a horse; ultrasound was used to monitor healing in tendon injuries in a group of race and sport horses treated with an experimental gene therapy designed to both speed healing and improve the quality of the healed injury site to prevent recurrence. (Image courtesy of University of Nottingham)

In October 2017, The Hoof Blog reported on experimental research looking into direct-injection gene therapy for soft tissue lameness injuries in horses. The authors of the 2017 paper had successfully cured lameness in two horses and published their results in the journal Frontiers in Veterinary Science.

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: https://www.frontiersin.org/articles/10.3389/fvets.2017.00168/full

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: albert.rizvanov@kpfu.ru.

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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Hoof Pathologist and Educator Dr. Roy Pool Honored by American College of Veterinary Pathologists

Today the American College of Veterinary Pathologists (ACVP) will bestow an honorary membership to Roy R. Pool Jr., PhD DVM, director of the Surgical Pathology Service and director of the Osteopathology Specialty Service at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM).

This award -- only given to a select few individuals -- will be presented to Dr. Pool for his many important contributions to his professional discipline over his more than 40-year career as a veterinary musculoskeletal pathologist at the ACVP's annual meeting.

Honorary membership is bestowed upon a nonmember by a majority vote of the Council, and confirmed by a majority vote of the membership of the College.

Over the years Pool has contributed a great deal to the understanding of the causes and pathological diagnosis of musculoskeletal diseases of domestic animals. A list of his research topics includes research on many species and especially the pathogenesis of biomechanical lesions of bone, joints, tendons, and ligaments of athletic horses.

Pool is the last of the original five veterinary musculoskeletal pathologists still active today in academic practice in this country. He has taught numerous courses, in several veterinary institutions across the United States and Europe including the University of California at Davis, Cornell University, and Mississippi State University.

Dr. Pool was recruited by the Texas A&M seven years ago where, in addition to his diagnostic duties, he teaches lectures in his specialty to professional students in the veterinary curriculum.

"Although I am a clinical professor of pathology with primary diagnostic and teaching responsibilities, I continue to be involved in orthopedic research (e.g. healing of defects in articular cartilage and in tendons facilitated by stem cells)," said Pool.

I will never forget meeting Dr. Pool. He was so interested in Hoofcare and Lameness, and I was so interested in a project he was working on, related to navicular disease. One of the first sentences out of his mouth was, "I just love the navicular bone!" and I could tell he meant it. He went on to tell me that he had collected hundreds of them, and that he never tired of looking at them. Over the years, he also has never seemed to tire of answering my questions, and offering advice for deeper reading or where to find someone who might know the answer to my question.

Dr. Pool opened his lecture at the AAEP convention in San Francisco with one of the best lines ever: "Some people collect stamps. I collect navicular bones!"

Hoofcare and Lameness has tried to keep up with Dr. Pool's research. In 1996, Hoofcare published a summary of 15 years of his equine research, Equine Joint Mechanics: An AAEP/H&L Report, after his presentation at the AAEP convention in Lexington, Kentucky.

In the 1980s, Dr. Pool was the first to notice the incidence of what was then called degenerative suspensory ligament desmitis (DSLD) when he was at the University of California at Davis. What may have been an observation on his part helped veterinarian Jan Young DVM formulate the first articles on the conditon, which were published in Hoofcare and Lameness. In 2002, he was the co-author with Dr Jeanette Mero of the paper, Twenty Cases of Degenerative Suspensory Ligament Desmitis in Peruvian Paso Horses, presented at that year's AAEP Convention in Orlando, Florida.

Not only students and the research community have benefited from Dr. Pool's research, his studies and his affection for the navicular bone--we all have benefited from his generosity and his curiosity. We should all give him an award for helping us understand what happens when something goes wrong with the musculoskeletal systems of athletic horses.

Thanks to Texas A&M University for assistance with this article.

© Fran Jurga and Hoofcare Publishing; Fran Jurga's Hoof Blog is a between-issues news service for subscribers to Hoofcare and Lameness Journal. Please, no use without permission. You only need to ask. This blog may be read online at the blog page, checked via RSS feed, or received via a digest-type email (requires signup in box at top right of blog page). To subscribe to Hoofcare and Lameness (the journal), please visit the main site, www.hoofcare.com, where many educational products and media related to equine lameness and hoof science can be found. Questions or problems with this blog? Send email to blog@hoofcare.com.

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