Gene Therapy for Osteoarthritis: Kinematic Analysis

Entry, Cases/Abstracts
Nichole Hughes, University of Florida

Steve Ghivizzani, MD; Patrick T. Colahan, DVM; Nichole Hughes
Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville FL
Department of Orthopedics and Rehabilitation, University of Florida College of Medicine,  Gainesville FL
Research supported by Merial

Osteoarthritis (OA) is one of the most prevalent diseases worldwide, causing chronic joint pain and progressive immobility due to the erosion of articular cartilage, subchondral bone sclerosis, and osteophyte formation. Though OA is widely unaffected by current treatments, experimentation has shown that local gene delivery of IL-1Ra (receptor antagonist) using scAAV (self-complimentary adeno-associated virus) vectors can have a significant effect in disease progression in animal models and allow sustained levels of IL-1Ra in the joint. This project uses kinematic analysis to evaluate the capacity of scAAV-mediated delivery of equine-IL-1Ra to block the development of experimental arthritis in the equine joint. To evaluate the therapeutic efficacy of scAAV-eqIL-1Ra, an osteochondral fragment (OCF) model is used to simulate the pathobiology of OA. After a recovery period, scAAV-eqIL-1Ra and placebo (saline) are delivered to the experimental and control groups, respectively. Motion analysis is conducted weekly on a high speed treadmill for 12 weeks. Quantifiable changes in kinematics are measured using Lameness Locator® software.

It is expected that local, intra-articular treatment with scAAV-eqIL-1Ra will provide protection from the development of the articular pathologies associated with OA.  Relative to placebo controls, treated animals should have reduced pain and improved mobility, thus resulting in a reduction in lameness as analyzed by the Lameness Locator. Thus far, only 5/20 horses have completed the project.  The kinematic analysis of these 5 horses shows that the placebo improves lameness at a rate 2.5 times faster than treatment with scAAV-eqIL-1Ra. However, it is too early to use these preliminary results to determine the overall efficacy of the therapy. Ultimately the final data from this part of the study will be compiled with MRI, radiography, arthroscopy, and data generated from recovered fluids and tissue biopsies to provide a comprehensive description of the effects of the gene based treatment. Based on these efficacy models in horses, we can gain insight on the use of gene transfer on a human scale as a therapy for osteoarthritis.

Case Report- Belgium Draft Nurse Mare with Chronic Progressive Lymphedema

Entry, Case Study
Rachel Ruden, University of Pennsylvania

History:

Lewie presented with gross lesions on both front fetlocks and a small cluster of nodules on the dorsal surface of her left hind pastern. The affected area was clearly painful. Her fetlocks were so swollen with edema it was hard to separate individual lesions, and they readily bled when manipulated. The odor and fluid attracted flies, but upon further examination, the moist spaces were also supporting colony of maggots. Finally, movement was onerous. All of these signs indicated Lewie was suffering from Chronic Progressive Lymphedema (CPL), commonly called Draft Horse Dermatitis. This is a skin disease that causes inflammation of the legs, most commonly affecting the fetlock region. Though the original insult may be a cut, the disease becomes escalated by secondary infections that produce edematous nodules that bleed and fester. Finally, ectoparasites complicate the issue, especially in mares that should not be treated with medications like Frontline while nursing. There is no cure for CPL, and due to its progressive and debilitating nature, this disease will put an early end to a horse’s career, and often, its life.

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There's a First for Everything

By: Megan Cassels-Conway

University of Georgia, Class of 2012

A first-hand account of Ruffian Equine Medical Center’s first extern and her first experience with orthopedic surgery

When you first get to an externship, you don’t really know what to expect. Of course, you’ve done your research- read the website, looked at brochures and talked to other students who have been there.  But what if you are the practice’s very first extern? How do you know what to expect?

            When I was looking for externships, a friend had told me about a new equine hospital that was being built in Long Island, NY. Living in northwest Pennsylvania, where I am originally from and spend my holidays and summers, there are no equine hospitals for hours. In fact, there are no equine vets at all within 90 minutes. Potential surgeries are taken five hours to the University of Pennsylvania or four hours to Cornell University Veterinary Schools. With the severe lack of opportunities for a hopeful equine surgeon, I was excited to hear about a state-of-the-art equine hospital being built five hours away.

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Colorfully Creative!

By: Lynda Mason

University of Florida, Class of 2014

Check out more of Lynda's artwork at http://www.horseofadifferentcolorart.com

"Candy Course"

"Fallen Idol"

"Road to Nowhere"

Savannah Sunrise

By: Carissa Hersum

Class of 2012, University of Minnesota