Posted June 16, 2020

Martha Murray, M.D., Boston Children’s Hospital, and Braden Fleming, Ph.D., Rhode Island Hospital

Osteoarthritis (OA) is a painful condition that results from the loss of cartilage in a patient’s joint, most commonly the hands, hips, and knees. The stiffness and swelling that can result from the loss of cartilage and increased inflammation commonly occur during aging (“degenerative OA”) as well as after an injury to the joint (“post-traumatic OA” [PTOA]). OA is one of the most common causes of disability in adults, and PTOA is the most common cause of disability in Service members.¹ In battlefield-injured Service members, PTOA was found to result in 100% of knee injuries within 2 years post-injury.¹ Currently, treatment options for OA are limited, including non-steroidal anti-inflammatory drugs widely used for pain relief and joint replacement surgery for end-stage disease.

A collaborative team of investigators at Boston Children’s Hospital and Rhode Island Hospital received a Military Medical Research and Development Award from the Joint Warfighter Medical Research Program (JWMRP) in 2016 to advance the development of a novel treatment for PTOA. The product, J-PRO, is an injectable extracellular matrix composite that can be mixed with a patient’s blood and injected into the injured joint to reduce the risk of development of PTOA.

Braden Fleming (left) and Martha Murray (right) research team

The investigative team, led by Dr. Martha Murray and Dr. Braden Fleming, has completed preliminary efficacy studies of J-PRO in a rat anterior cruciate ligament (ACL) transection model comparing a phosphate buffered saline (PBS) (control) injection to J-PRO administration. After 6 weeks of healing, hind limbs were retrieved and assessed by histology. While the ACL transection followed by a PBS injection led to significant structural damage, this was not seen following the ACL transection followed by an injection of J-PRO (Figure 1). Severe PTOA developed in 20% of the knees that received PBS injection compared to only 5% that received J-PRO. The team is now moving forward to assess J-PRO in additional preclinical models of OA.

With their JWMRP support, the investigative team has been working with the U.S. Food and Drug Administration (FDA) toward establishing a regulatory pathway for J-PRO. The team is compiling the necessary preclinical information including manufacturing, biocompatibility, and stability studies, to support their FDA application and ultimately receive approval for a first-in-human clinical trial of J-PRO.

Figure 1. Histology of the medial tibial plateau 6 weeks after ACL transection surgery.
Left: Control knee (no surgery). Middle: A knee that had an ACL transection followed by a PBS injection. Right: A knee that had an ACL transection followed by an injection of J-PRO.

¹ Rivera JC, Wenke JC, Buckwalter JA, Ficke JR, Johnson AE. 2012. Posttraumatic osteoarthritis caused by battlefield injuries: the primary source of disability in warriors. J Am Acad Orthop Surg. 20:1(0 1):S64‐S69. doi:10.5435/JAAOS-20-08-S64.

Link:

Public and Technical Abstracts: Lyophilized Injectable for Point-of-Care Therapeutic for Post-Traumatic Osteoarthritis

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