mdHACM Allografts Demonstrate Potential in Treating Knee Osteoarthritis

Osteoarthritis (OA) is a degenerative disease that occurs when the cartilage within a joint begins to deteriorate, resulting in biomechanical changes, including to the subchondral bone. OA is the most common form of arthritis, affecting more than 32.5 million U.S. adults¹ and 300 million people worldwide.² Those suffering from OA can experience stiffness, decreased range of motion and swelling, often in the hands, feet, hips, knees, and spine.

While there is no cure for OA, most current therapies—short of surgery—merely provide temporary symptomatic relief rather than addressing the underlying cause. Current non-surgical OA treatments, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and hyaluronic acid (HA) injections, relieve acute pain and reduce inflammation instead of addressing degenerative structural damage to the articular cartilage (AC). Some HA formulations require multiple injections, with mixed data on clinical efficacy, while long-term steroid use has well-recognized complications.

The causes of OA are multi-factorial and incompletely understood; effective treatments may be required to target many different pathways. Previous attempts to develop a small molecule therapeutic with disease-modifying activity have been largely ineffective, in part due to the complex nature of the disease pathogenesis, involving dysregulation of multiple signaling pathways.

Targeting OA Pathways
Two fundamental molecular signaling pathways implicated in OA-driven AC degeneration are Wnt/β-catenin and NF-κβ. These pathways are thought to be dysregulated in OA; thus, there is a therapeutic effort to potentially normalize both.

PURION processed micronized dehydrated human amnion chorion membrane (mdHACM), an investigational biologic, presents a unique approach to targeting multiple pathways. Proteomic analysis of mdHACM has identified more than 300 regulatory proteins, which are inherent to native amniotic tissues.

I co-authored a recent study in Osteoarthritis and Cartilage Open highlighting research developing in-vitro systems to model aspects of OA through elevated Wnt/β-catenin and NF-κβ signaling in 3D chondrocyte pellet-cultures and synoviocytes.³ Treatment with mdHACM in this “diseased” state regulated both signaling pathways, normalizing the inflammatory cascade and expression of key enzymes responsible for cartilage degradation.

Together with our previous in vivo data,⁴ this study supports a novel mechanism of action where mdHACM regulates both NF-κβ and canonical Wnt signaling to elicit a chondroprotective effect. The results show potential for mdHACM in attenuating OA progression.

This biologic is an attractive therapeutic candidate for several reasons. First, it has a strong safety profile and is easily administered in the clinician’s office. mdHACM also may be a beneficial alternative treatment for patients who are unsuitable candidates for invasive surgical procedures such as joint replacement. Moreover, the potential for mdHACM to modify the course of the disease, may delay the need for surgical intervention. It is important to note that rigorous clinical trials will be necessary to correlate in-vitro data to clinical relevance, as well as to qualify mdHACM for an indication to treat the disease.

Looking Ahead
Continuing efforts are underway to further evaluate mdHACM’s role in targeting additional implicated pathways and regulating OA progression. Registrational clinical trials of mdHACM in knee OA are planned to begin this year with the goal of gaining FDA approval in 2026. The hope is to deliver a novel therapeutic that addresses a significant unmet medical need posed by degenerative musculoskeletal conditions, beginning with knee osteoarthritis. It is an exciting time for the field as investigators study new regenerative biologics with the potential to improve the lives of millions of patients.

References
¹ Osteoarthritis (OA). Centers for Disease Control and Prevention. Updated July 27, 2020. Accessed April 28, 2022. https://www.cdc.gov/arthritis/basics/osteoarthritis.htm#signs 
² Safiri S, Kolahi A, Smith E, et al. Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017. Ann Rheum Dis. 2020;79(6):819-828. Published 12 May 2020. doi: 10.1136/annrheumdis-2019-216515 
³ Chung C, Massee M, Koob TJ. Human amniotic membrane modulates Wnt/β-catenin and NF-κβ signaling pathways in articular chondrocytes in vitro. Osteoarthritis and Cartilage Open. 2021;3(4):100211. Published 2021 Dec. doi: 10.1016/j.ocarto.2021.100211
⁴ Willett NJ, Thote T, Lin AS, et al. Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development. Arthritis Res Ther. 2014;16(1):R47. Published 2014 Feb 6. doi:10.1186/ar4476

Michelle Massee was appointed associate vice president of Product Development at MIMEDX in July 2021. She joined the company in 2010, taking on roles of increasing responsibility within the research department, previously serving as associate vice president of Research. During her 11-year tenure, she advanced the science of the MIMEDX placental-based platform, publishing numerous manuscripts on mechanism of action. Her recent transition into product development is intended to leverage her scientific understanding to expand the MIMEDX product portfolio. Massee earned her bachelor of science degree in biomedical engineering at the Georgia Institute of Technology.