Gene Therapy, Stem Cells' Effects on Equine Osteoarthritis

Gene Therapy, Stem Cells' Effects on Equine Osteoarthritis

A combination of mesenchymal stem cells (seen here) and gene therapy reduced osteoarthritis progression in Watts' model.

Photo: The Horse Staff

The adage says that two heads are better than one. And when it comes to treating equine osteoarthritis, researchers recently showed that two methods—dual-axis gene therapy and mesenchymal stem cells (MSCs)—might also be better than one.

Ashlee Watts, DVM, PhD, Dipl. ACVS, an assistant professor at the Texas A&M College of Veterinary Medicine & Biomedical Sciences, presented the results of her study on the topic at the 2013 American Association of Equine Practitioners' Convention, held Dec. 7-11 in Nashville, Tenn.

Osteoarthritis (OA) is a painful, incurable condition primarily characterized by the progressive destruction of articular cartilage. Veterinarians currently have many symptomatic treatment options—which relieve clinical signs, but don't stop the disease for progressing—such as non-steroidal anti-inflammatory drug therapy. Their disease-modifying treatment options—those that slow, stop, or reverse the degenerative process—for the condition are much more limited, however.

In their recent study, Watts and colleagues tested a combination of dual-axis gene therapy and stem cells injected intra-articularly (directly into the joint) for treating early-stage OA. "Dual axis means that we were utilizing gene therapy to augment stem cells to reduce catabolic (destructive) and increase anabolic (healing) pathways within the joint," she explained.

While gene therapy—using genes to treat or prevent disease—is still in its infancy in equine medicine, stem cell therapy has been used extensively in treating equine injuries. MSCs are multipotent stromal (connective tissue) cells that can differentiate into many types of cells, including those that make up bone, cartilage, and fat.

Watts said the MSCs used in her study overexpressed the anabolic transforming growth factor (TGF)-β3, concurrent with an RNA interference motif to suppress the catabolic interleukin (IL)-1β and tumor necrosis factor (TNF)-?.

Sound confusing? She explained this in simpler terms: "This means that TGF-β3 would be produced more than it would have been by the cells without gene therapy. It is an anabolic (building/healing) growth factor and increased production of TGF-β3 should improve soft tissue healing and reduce scar tissue formation.

"IL-1β (same protein we are targeting with IRAP [or interleukin-1 receptor antagonist protein] treatment, where we are trying to block cell receptors for IL-1β) is a catabolic (destructive/pro-inflammatory) factor," she continued. "Gene knockdown via RNA interference means that we use gene therapy to reduce the cells' production of IL-1β, thereby reducing inflammation. This might be more complete reduction of IL-1β compared to IRAP, where we are competitively binding IL-1β receptors to reduce inflammation."

In their study, Watts and colleagues employed 13 mature Thoroughbreds with experimentally induced early-stage OA in the middle carpal bone (located in the knee). Six horses received the MSC and gene therapy injections in the affected joints (also 14 days after induction), while seven horses received placebo injections 14 days after OA induction.

Key study results included:

  • The researchers did not observe any adverse effects of treatment with MSCs and gene therapy;
  • In the week following treatment the team observed significant improvements in range of motion and joint swelling in joints treated with MSCs and gene therapy compared to control joints;
  • They also identified significantly higher glycosaminoglycan (which protect degenerating cartilage) levels in the opposing knee bone cartilage, improved cartilage matrix (which is responsible for absorbing shock during weight bearing) gene expression, and synovial membrane (membrane lining the joint) IL-1β in treated joints compared to control joints; and
  • Treated joints had reduced synovial fibrosis (scarring) compared to placebo-injected joints.

Essentially, Watts said, this combination of MSCs and gene therapy reduced OA progression in this model.

She noted that this treatment protocol still needs to undergo further testing before it is available for use in clinical practice. "It is possible that the stem cells themselves had a major treatment effect and it was not the addition of gene therapy that led to the improvements seen," she said. "Therefore, the experiment should be repeated with the addition of a third group that receive stem cells only."

About the Author

Erica Larson, News Editor

Erica Larson, news editor, holds a degree in journalism with an external specialty in equine science from Michigan State University in East Lansing. A Massachusetts native, she grew up in the saddle and has dabbled in a variety of disciplines including foxhunting, saddle seat, and mounted games. Currently, Erica competes in eventing with her OTTB, Dorado.

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