Novel Therapy for Equine Osteoarthritis: pPRP-Lysate

Osteoarthritis (OA) remains the leading cause of lameness and poor performance in the horse industry, presenting a huge problem in equine clinical practice. Although many therapies are available, none has proven a reliable and effective treatment for this as-yet incurable disease. One recently described product, pooled platelet-rich plasma lysate (pPRP-L), has drawn attention and holds promise as a novel disease-modifying therapy. pPRP-L could “substantially change the treatment of OA because of its ability to increase hyaluronic acid and cartilage extracellular matrix production while dampening inflammation,” said North Carolina State University researcher Lauren Schnabel, DVM, PhD, Dipl. ACVS ACVSMR.

“Platelet-rich plasma lysate is produced by collecting platelets from a horse’s blood sample, concentrating them, then breaking open those platelets to release all the growth factors and anti-inflammatory mediators,” Schnabel explained during her presentation during the 2020 American Association of Equine Practitioners’ Convention, held virtually. “Platelet lysates (from multiple horses) can be combined to produce a pooled product that is more robust than a sample from a single horse.”

A hallmark of OA is inflammation of the inner lining of the joint called the synovial membrane. In the face of inflammation, hyaluronic acid (HA), a key component of joint fluid, shifts from a high molecular weight molecule to an inferior low molecular weight molecule that can’t adequately protect the cartilage, resulting in even more inflammation and joint damage.

“Previous work by our lab has shown that pPRP-L significantly increases HA production,” Schnabel said. “The mechanism by which this increased HA occurred, however, was unclear.”

Therefore, the researchers wanted to determine if pPRP-L was increasing production of high molecular weight HA through gene expression of the enzyme hyaluronic synthase (HAS)2  as compared to the inferior low molecular weight HA through gene expression of HAS3.

Continuing their research, Schnabel and colleagues created cultures of cartilage and synovial cells in the lab. They induced inflammation similar to what a practitioner might observe in a live horse’s joint with OA. They treated the cultures with either an exogenous (from a different individual) source of HA, a steroid called triamcinolone used to treat OA in live horses, pPRP-L, or no treatment at all.

Key findings of the study included:

  • pPRP-L significantly increased the gene expression of HAS2 responsible for high molecular weight HA production compared to all other treatments and controls without causing increased HAS3 gene expression responsible for low molecular weight HA production;
  • pPRP-L significantly decreased production of the pro-inflammatory mediators interleukin-1b (IL-1b) and matrix metalloproteinase-13 (MMP-13) compared to the control cultures. The level of decrease they observed was equivalent to that seen with the potent anti-inflammatory triamcinolone; and
  • pPRP-L also significantly increased cartilage extracellular matrix production by cartilage cells compared to all other treatments and controls.

“Together, these results show that pPRP-L can restore normal HA synthesis and cartilage extracellular matrix production in the face of inflammation,” Schnabel said. “This offers a unique anti-inflammatory approach to joint preservation.”

She said the next step is to identify individual components of the pooled PRP lysate that might be responsible for these beneficial effects, so they can design even more targeted treatments for OA that can be scaled up for manufacturing and distribution.