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The journal of gene medicine2008; 10(5); 564-574; doi: 10.1002/jgm.1170

Plasmid growth hormone releasing hormone therapy in healthy and laminitis-afflicted horses-evaluation and pilot study.

Abstract: In vivo electroporation dramatically improves the potency of plasmid-mediated therapies, including in large animal models. Laminitis and arthritis are common and debilitating diseases in the horse, as well as humans. Methods: The effects of growth hormone releasing hormone (GHRH) on healthy horses and on horses with laminitis that were followed for 6 months after a single intramuscular injection and electroporation of 2.5 mg of an optimized myogenic GHRH-expressing plasmid were examined. Results: In the first study on six healthy horses, we observed a significant increase in body mass by day 180 compared to baseline (P < 0.003), and an increase in erythrocyte production (hematocrit, red blood cells, hemoglobin, P = 0.03). IGF-I levels were increased by 7% by day 120 (P = 0.02). A pilot study was performed on two horses with chronic laminitis, a vascular condition often associated with arthritis, with two horses with similar clinical disease serving as non-treated controls. Treated horses experienced an increase in weight compared to control horses that received standard care (P = 0.007). By 6 months post-treatment, treated subjects were rated pasture sound. Physical and radiographic evaluation demonstrated significant improvement with reduced inflammation and decreased lameness. Conclusions: These results demonstrate that a plasmid therapy delivered by electroporation can potentially be used to treat chronic conditions in horses, and possibly other very large mammals. While further studies are needed, overall this proof-of-concept work presents encouraging data for studying gene therapeutic treatments for Raynaud's syndrome and arthritis in humans.
Publication Date: 2008-02-28 PubMed ID: 18302303DOI: 10.1002/jgm.1170Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research paper discusses a pilot study on the effects of a treatment method using growth hormone releasing hormone (GHRH) on both healthy horses and those suffering from laminitis, a debilitating disease common in horses. The reported outcomes indicate that this therapy improved the health and physique of the subjects and could potentially be suitable for treating long-term conditions in large mammals, providing preliminary evidence in the realm of gene therapeutic treatments for human diseases like Raynaud’s syndrome and arthritis.

Methods

  • The researchers used in vivo electroporation, a technique that increases the effectiveness of plasmid-mediated therapies. In this case, the therapy administered was a plasmid that expressed the growth hormone releasing hormone (GHRH).
  • The method involved a single intramuscular injection, followed by electroporation, of 2.5 mg of the GHRH-expressing plasmid.
  • The procedure’s impacts were observed in two groups of horses – six healthy horses and two horses that suffered from chronic laminitis, a vascular condition often associated with arthritis. The study followed the progress of the subjects for a period of 6 months.

Results

  • In the healthy horses examined in the study, the researchers observed an increase in body mass by day 180 as compared to the baseline, with the difference being statistically significant.
  • A significant increase was also seen in the erythrocyte (red blood cells) production, measured in terms of hematocrit, red blood cells count, and hemoglobin levels.
  • Another significant finding was the 7% increase in IGF-I levels by day 120.
  • The laminitis-afflicted horses that received the treatment showed weight gain compared to the control horses (which did not receive the treatment). By the end of the 6-month period, these treated horses were assessed to be pasture sound. These horses also showed visible physical and radiographic improvements, including reduced inflammation and decreased lameness.

Conclusions

  • The findings of this exploratory study point towards the potential of plasmid therapy, delivered through electroporation, in treating chronic conditions in large mammals, such as horses.
  • The positive effects of the treatment open up possibilities for its application in gene therapeutic treatments for human ailments such as Raynaud’s syndrome and arthritis. However, it’s crucial to remember that these are preliminary findings, and further studies are required to ascertain the full potential and applicability of the method.

Cite This Article

APA
Brown PA, Bodles-Brakhop A, Draghia-Akli R. (2008). Plasmid growth hormone releasing hormone therapy in healthy and laminitis-afflicted horses-evaluation and pilot study. J Gene Med, 10(5), 564-574. https://doi.org/10.1002/jgm.1170

Publication

ISSN: 1521-2254
NlmUniqueID: 9815764
Country: England
Language: English
Volume: 10
Issue: 5
Pages: 564-574

Researcher Affiliations

Brown, Patricia A
  • VGX Animal Health, The Woodlands, Texas 77381, USA.
Bodles-Brakhop, Angela
    Draghia-Akli, Ruxandra

      MeSH Terms

      • Animals
      • Arthritis / therapy
      • Electroporation
      • Genetic Therapy / methods
      • Growth Hormone-Releasing Hormone / administration & dosage
      • Horse Diseases / therapy
      • Horses
      • Injections, Intramuscular
      • Models, Animal
      • Pilot Projects
      • Plasmids / administration & dosage
      • Treatment Outcome

      Citations

      This article has been cited 6 times.
      1. Qin YJ, Chan SO, Chong KK, Li BF, Ng TK, Yip YW, Chen H, Zhang M, Block NL, Cheung HS, Schally AV, Pang CP. Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation. Proc Natl Acad Sci U S A 2014 Dec 23;111(51):18303-8.
        doi: 10.1073/pnas.1421815112pubmed: 25489106google scholar: lookup
      2. Khan AS, Draghia-Akli R, Shypailo RJ, Ellis KI, Mersmann H, Fiorotto ML. A comparison of the growth responses following intramuscular GHRH plasmid administration versus daily growth hormone injections in young pigs. Mol Ther 2010 Feb;18(2):327-33.
        doi: 10.1038/mt.2009.224pubmed: 19809401google scholar: lookup
      3. Koch TG, Berg LC, Betts DH. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine. Can Vet J 2009 Feb;50(2):155-65.
        pubmed: 19412395
      4. Bodles-Brakhop AM, Heller R, Draghia-Akli R. Electroporation for the delivery of DNA-based vaccines and immunotherapeutics: current clinical developments. Mol Ther 2009 Apr;17(4):585-92.
        doi: 10.1038/mt.2009.5pubmed: 19223870google scholar: lookup
      5. Brown PA, Bodles-Brakhop AM, Pope MA, Draghia-Akli R. Gene therapy by electroporation for the treatment of chronic renal failure in companion animals. BMC Biotechnol 2009 Jan 16;9:4.
        doi: 10.1186/1472-6750-9-4pubmed: 19149896google scholar: lookup
      6. Young KAS, Schnabel LV, Gilger BC. Cell and Gene Therapy in Equine Ocular Disease. Vet Ophthalmol 2026 Mar;29(2):e70151.
        doi: 10.1111/vop.70151pubmed: 41623202google scholar: lookup