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Frontiers in veterinary science2017; 4; 168; doi: 10.3389/fvets.2017.00168

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.

Abstract: In this clinical study, for the first time we used the direct gene therapy to restore severe injuries of the suspensory ligament branch and superficial digital flexor tendon in horses (). We injected the plasmid DNA encoding two therapeutic species-specific growth factors: vascular endothelial growth factor 164 and fibroblast growth factor 2 at the site of injury in the suspensory ligament branch and tendon. Treatment effects were evaluated with the use of clinical observation and ultrasound imaging during a period of a few months. 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.
Publication Date: 2017-10-10 PubMed ID: 29067288PubMed Central: PMC5641304DOI: 10.3389/fvets.2017.00168Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research reveals that gene therapy involving the injection of DNA encoding two growth factors can effectively treat severe injuries in horse tendons and ligaments, leading to functional recovery and complete restoration of the damaged tissues.

Objectives of the Study

  • The study sought to use direct gene therapy to heal severe injuries of the suspensory ligament branch and superficial digital flexor tendon in horses.
  • They aimed to do this by injecting plasmid DNA encoding two therapeutic species-specific growth factors: vascular endothelial growth factor 164 and fibroblast growth factor 2.
  • The effectiveness of this treatment was to be evaluated through clinical observation and ultrasound imaging over a period of several months.

Procedure and Evaluation

  • The method applied in this study involved the administration of gene therapy using plasmid DNA encoding the specific growth factors directly at the site of the horse’s injury.
  • After the treatment was administered, the horses’ clinical progress was regularly monitored and evaluated over a few months.
  • Ultrasound imaging was used as a tool to examine the level of healing and restoration in the damaged suspensory ligament and tendon.

Findings of the Study

  • The results from the study demonstrated that the use of gene therapy in a period of 2-3 months after the injury led to complete recovery of functions in the horses.
  • Additionally, the study also showed full restoration of the severely damaged suspensory ligament and superficial digital flexor tendon in the horses.
  • Thus, the findings from this research show promising implications in the field of veterinary medicine, particularly for the treatment of severe ligament and tendon injuries in horses.

Cite This Article

APA
Kovac M, Litvin YA, Aliev RO, Zakirova EY, Rutland CS, Kiyasov AP, Rizvanov AA. (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. Front Vet Sci, 4, 168. https://doi.org/10.3389/fvets.2017.00168

Publication

ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 4
Pages: 168
PII: 168

Researcher Affiliations

Kovac, Milomir
  • Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, Russia.
Litvin, Yaroslav A
  • Kazan Federal University, Kazan, Russia.
Aliev, Ruslan O
  • Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, Russia.
Zakirova, Elena Yu
  • Kazan Federal University, Kazan, Russia.
Rutland, Catrin S
  • Faculty of Medicine, School of Veterinary Medicine and Science, University of Nottingham, Nottingham, United Kingdom.
Kiyasov, Andrey P
  • Kazan Federal University, Kazan, Russia.
Rizvanov, Albert A
  • Kazan Federal University, Kazan, Russia.

References

This article includes 19 references
  1. Kovac M, Nowak M, Küpers S, Tambur Z. Frequency of orthopedic diseases in horses: a retrospective study.. Vet Glas (2002) 56:307–19.
    doi: 10.2298/VETGL0206307Kgoogle scholar: lookup
  2. Riley G. The pathogenesis of tendinopathy. A molecular perspective.. Rheumatology (Oxford) 2004 Feb;43(2):131-42.
    doi: 10.1093/rheumatology/keg448pubmed: 12867575google scholar: lookup
  3. Clegg PD, Strassburg S, Smith RK. Cell phenotypic variation in normal and damaged tendons.. Int J Exp Pathol 2007 Aug;88(4):227-35.
  4. Kearney RS, Parsons N, Metcalfe D, Costa ML. Injection therapies for Achilles tendinopathy.. Cochrane Database Syst Rev 2015 May 26;(5):CD010960.
  5. Uysal CA, Tobita M, Hyakusoku H, Mizuno H. Adipose-derived stem cells enhance primary tendon repair: biomechanical and immunohistochemical evaluation.. J Plast Reconstr Aesthet Surg 2012 Dec;65(12):1712-9.
    doi: 10.1016/j.bjps.2012.06.011pubmed: 22771087google scholar: lookup
  6. Middleton KK, Barro V, Muller B, Terada S, Fu FH. Evaluation of the effects of platelet-rich plasma (PRP) therapy involved in the healing of sports-related soft tissue injuries.. Iowa Orthop J 2012;32:150-63.
    pmc: PMC3565396pubmed: 23576936
  7. Martinek V, Huard J, Fu FH. Gene therapy in tendon ailments.. Tendon Inj Basic Sci Clin Med (2005) p. 307–12.
    doi: 10.1007/1-84628-050-8_30google scholar: lookup
  8. Litvin YA, Zakirova EY, Zhuravleva MN, Rizvanov AA. Generation of plasmid DNA expressing species-specific horse VEGF164 and FGF2 factors for gene therapy.. Bionanoscience (2016) 6:550–3.
    doi: 10.1007/s12668-016-0273-2google scholar: lookup
  9. FDA. Considerations for Plasmid DNA Vaccines for Infectious Disease Indications.. USA: Food and Drug Administration; (2007). p. 1–18.
  10. FDA. Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs).. USA: Food and Drug Administration; (2008). p. 1–89.
  11. EMA. Reflection Paper on Design Modifications of Gene Therapy Medicinal Products during Development.. London: European Medicines Agency; (2001). p. 1–9.
  12. EMA. Guideline on the Non-Clinical Studies Required before First Clinical Use of Gene Therapy Medicinal Products.. London: European Medicines Agency; (2008). EMEA/CHMP/GTWP/125459/2006.
  13. Zakirova EY, Vasin NN, Zhuravleva MN, Rizvanov AA. Case report of application gene construction with VEGF and BMP2 in restoration of tear in the anterior cruciate ligament of a large breed dog.. Genes Cells (2014) 9:93–5.
  14. Plotnikov MV, Rizvanov AA, Masgutov RF, Mavlikeev MO, Salafutdinov II, Gazizov IM. The first clinical experience of direct gene therapy using VEGF and bFGF in treatment patients with critical lower limb ischemia.. Cell Transplant Tissue Eng (2012) 7:180–4.
  15. Evans CH, Ghivizzani SC, Robbins PD. Orthopedic gene therapy in 2008.. Mol Ther 2009 Feb;17(2):231-44.
    doi: 10.1038/mt.2008.265pmc: PMC2835052pubmed: 19066598google scholar: lookup
  16. Tang JB, Wu YF, Cao Y, Chen CH, Zhou YL, Avanessian B, Shimada M, Wang XT, Liu PY. Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons.. Sci Rep 2016 Feb 11;6:20643.
    doi: 10.1038/srep20643pmc: PMC4749961pubmed: 26865366google scholar: lookup
  17. Byrne AM, Bouchier-Hayes DJ, Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF).. J Cell Mol Med 2005 Oct-Dec;9(4):777-94.
  18. Deev R, Plaksa I, Bozo I, Isaev A. Results of an International Postmarketing Surveillance Study of pl-VEGF165 Safety and Efficacy in 210 Patients with Peripheral Arterial Disease.. Am J Cardiovasc Drugs 2017 Jun;17(3):235-242.
    doi: 10.1007/s40256-016-0210-3pmc: PMC5435773pubmed: 28050885google scholar: lookup
  19. Deev RV, Bozo IY, Mzhavanadze ND, Voronov DA, Gavrilenko AV, Chervyakov YV, Staroverov IN, Kalinin RE, Shvalb PG, Isaev AA. pCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for Patients With Chronic Lower Limb Ischemia.. J Cardiovasc Pharmacol Ther 2015 Sep;20(5):473-82.
    doi: 10.1177/1074248415574336pubmed: 25770117google scholar: lookup

Citations

This article has been cited 8 times.
  1. Tozaki T, Ohnuma A, Kikuchi M, Ishige T, Kakoi H, Hirota KI, Takahashi Y, Nagata SI. Investigation of optimal procedures for storage and use of plasma samples suitable for gene doping tests.. J Equine Sci 2023 Jun;34(2):21-27.
    doi: 10.1294/jes.34.21pubmed: 37405066google scholar: lookup
  2. Liu X, Zhu B, Li Y, Liu X, Guo S, Wang C, Li S, Wang D. The Role of Vascular Endothelial Growth Factor in Tendon Healing.. Front Physiol 2021;12:766080.
    doi: 10.3389/fphys.2021.766080pubmed: 34777022google scholar: lookup
  3. Aimaletdinov A, Mindubaeva G, Khalikova S, Kabwe E, Salmakova A, Alexandrova N, Rutland C, Rizvanov A, Zakirova E. Application of gene therapy in the treatment of superficial digital flexor tendon injury in horses.. Open Vet J 2020 Oct;10(3):261-266.
    doi: 10.4314/ovj.v10i3.3pubmed: 33282696google scholar: lookup
  4. Zakirova EY, Shalimov DV, Garanina EE, Zhuravleva MN, Rutland CS, Rizvanov AA. Use of Biologically Active 3D Matrix for Extensive Skin Defect Treatment in Veterinary Practice: Case Report.. Front Vet Sci 2019;6:76.
    doi: 10.3389/fvets.2019.00076pubmed: 30931318google scholar: lookup
  5. Tozaki T, Ohnuma A, Takasu M, Kikuchi M, Kakoi H, Hirota KI, Kusano K, Nagata SI. Droplet Digital PCR Detection of the Erythropoietin Transgene from Horse Plasma and Urine for Gene-Doping Control.. Genes (Basel) 2019 Mar 21;10(3).
    doi: 10.3390/genes10030243pubmed: 30901981google scholar: lookup
  6. Tozaki T, Gamo S, Takasu M, Kikuchi M, Kakoi H, Hirota KI, Kusano K, Nagata SI. Digital PCR detection of plasmid DNA administered to the skeletal muscle of a microminipig: a model case study for gene doping detection.. BMC Res Notes 2018 Oct 10;11(1):708.
    doi: 10.1186/s13104-018-3815-6pubmed: 30309394google scholar: lookup
  7. Kovac M, Litvin YA, Aliev RO, Zakirova EY, Rutland CS, Kiyasov AP, Rizvanov AA. Gene Therapy Using Plasmid DNA Encoding VEGF164 and FGF2 Genes: A Novel Treatment of Naturally Occurring Tendinitis and Desmitis in Horses.. Front Pharmacol 2018;9:978.
    doi: 10.3389/fphar.2018.00978pubmed: 30233367google scholar: lookup
  8. Gyles C. The promise of gene therapy.. Can Vet J 2018 Jun;59(6):571-574.
    pubmed: 29910471