Class
Article
College
College of Agriculture and Applied Sciences
Department
School of Veterinary Medicine
Faculty Mentor
Jeff Mason
Presentation Type
Oral Presentation
Abstract
Equine laminitis is a condition that results in lameness, extreme pain, and in many cases, concludes in euthanasia. The epidermal and dermal layers of the hoof's lamina are stabilized by connective tissues. Homeostatic metabolic factors allow for healthy remodeling of the lamina. When laminitis occurs, the enzymes that degrade lamellar connective tissue are upregulated while the concentration of degradative inhibitors (TIMP-3) is not changed. The unbalanced state of the metabolic factors compromises the structural integrity of the lamina and allows for movement of the coffin bone within the hoof capsule. Gene therapy has manifested promising results for preventing laminitis. The current study used recombinant adeno-associated viral vectors (rAAVs) to deliver a therapeutic TIMP-3 transgene to healthy lamellar tissues. Venography was used to visualize the vasculature and evaluate tissue uptake. Hoof tissue samples were harvested for analysis post-injection. We have found that the tissues of the foot were transduced with the therapeutic TIMP-3 gene and we expect to find that the TIMP-3 protein has been produced endogenously by transfected cells. The increased endogenous production of TIMP-3 could restore lamellar metabolic homeostasis within a laminitic hoof. Favorable results of this study will allow for future clinical trials which evaluate the effects of gene therapy on equine laminitis.
Location
Room 101
Start Date
4-11-2019 9:00 AM
End Date
4-11-2019 10:15 AM
Included in
Employing Recombinant Adeno-associated Viral Vectors for Delivery of a Therapeutic TIMP-3 Transgene to the Equine Distal Extremity
Room 101
Equine laminitis is a condition that results in lameness, extreme pain, and in many cases, concludes in euthanasia. The epidermal and dermal layers of the hoof's lamina are stabilized by connective tissues. Homeostatic metabolic factors allow for healthy remodeling of the lamina. When laminitis occurs, the enzymes that degrade lamellar connective tissue are upregulated while the concentration of degradative inhibitors (TIMP-3) is not changed. The unbalanced state of the metabolic factors compromises the structural integrity of the lamina and allows for movement of the coffin bone within the hoof capsule. Gene therapy has manifested promising results for preventing laminitis. The current study used recombinant adeno-associated viral vectors (rAAVs) to deliver a therapeutic TIMP-3 transgene to healthy lamellar tissues. Venography was used to visualize the vasculature and evaluate tissue uptake. Hoof tissue samples were harvested for analysis post-injection. We have found that the tissues of the foot were transduced with the therapeutic TIMP-3 gene and we expect to find that the TIMP-3 protein has been produced endogenously by transfected cells. The increased endogenous production of TIMP-3 could restore lamellar metabolic homeostasis within a laminitic hoof. Favorable results of this study will allow for future clinical trials which evaluate the effects of gene therapy on equine laminitis.