On September 22, 2022, watch NIH VideoCast - Cartilage Preservation and Restoration for Knee Osteoarthritis.

See the NIH Record article: "NIAMS Hosts Roundtable on Regenerative Medicine in Knee OA"

Background

Current medicinal treatments for knee osteoarthritis (OA) do not modify the disease course. A major barrier to the development of disease-modifying interventions is the nature of knee OA progression, where initial articular cartilage damage triggers a vicious cycle of molecular events and tissue interactions in a downward spiral and rapidly progresses to diffuse knee OA. Stopping this elaborate process is a challenge, making preservation and restoration of articular cartilage a critical topic of investigation.

Regenerative medicine is an emerging area of science that holds great promise for treating and even curing a variety of injuries and diseases. Over the last decade, a variety of regenerative medicine approaches that either preserve articular cartilage in people who started with a focal cartilage injury and thus are at a higher risk of developing knee OA or restore defective articular cartilage in patients with symptomatic knee OA have been investigated. The clinical use of biologics, including intra-articular injections of platelet-rich plasma (PRP) and bone marrow- or tissue-derived mesenchymal stem cells (MSC), are becoming increasingly prevalent as treatment strategies for patients with knee OA. Some molecules such as fibroblast growth factor (FGF) and exogenous cartilage matrixes that can be fixated over the perforated subchondral bone and act as scaffolds for released MSC and growth factors are in late stages of clinical development and show promise for knee OA. Moreover, extracellular vesicles [either microvesicles (MVs) or exosomes (Exo)] and gene therapy have improved repair in animal studies. Such progresses notwithstanding, much work remains to be done toward the development of safe and effective regenerative medicine products.

In addition to the barrier noted above, therapeutic development for knee OA has been constrained by several factors including disease heterogeneity, the multitude of knee OA risk factors, the poor association between structural changes and clinically meaningful endpoints, discordances between preclinical and human models, and regulatory hurdles. Biologic therapies, for example, continue to be debated as a definitive treatment for symptomatic knee OA, although some clinical studies have demonstrated that they are relatively safe and lead to significant improvement of clinical and functional outcomes and patient’s quality of life. This debate is partially due to a lack of evidence from robust, well-designed clinical trials with reproducible methodology. Most level I evidence studies so far have issues such as small sample sizes, potentially inappropriate control cohorts, or relatively short-term follow-ups. Most importantly, there are also concerns regarding the heterogeneity and lack of standardization and consensus in the optimal preparations, source, delivery methods, and dosing of biologics for therapy. In July 2020, the U.S. Food and Drug Administration published guidance on the “Minimal Manipulation and Homologous Use” of cell and tissue products. With stricter interpretation of minimal manipulation and homologous use criteria for cell-based therapies from the FDA, many cell-based therapies that used to be self-designated as belonging to the 361 pathway (which is less regulated and not required to have clinical data) are likely to be reclassified as belonging to the 351 regulatory pathway (which is more regulated and required to have clinical data).

Purpose

Recognizing the great promise of regenerative medicine for the treatment of knee OA, the importance of promoting scientific rigor and protecting patient safety, and the timing for the extramural community to adapt to the new FDA guidance, NIAMS is organizing a roundtable to engage stakeholders to discuss challenges, gaps, and opportunities regarding regenerative medicine approaches for cartilage preservation and restoration in knee OA and where and how NIAMS could play a role and move the field forward. Stakeholders include investigators with expertise in regenerative medicine, experts in clinical treatment of knee OA, and FDA representatives.

Agenda

NIAMS Roundtable on Cartilage Preservation and Restoration in Knee Osteoarthritis (OA) DRAFT Agenda

September 22, 2022

Evidence, Challenges, Gaps, and Opportunities

12:50 - 1:20 PM – Group Photo and Lunch Break

3:00 - 3:15 PM – Break

Participants

BAJPAYEE, Ambika, Ph.D., M.Eng., Northwestern University

BARRY, Frank, Ph.D., Colorado State University

BRYANT, Stephanie, Ph.D., University of Colorado, Boulder

BUXTON, Denis, Ph.D., National Heart, Lung, and Blood Institute

CHU, Constance, M.D., Stanford University (co-chair)

ELISSEEFF, Jennifer, Ph.D., Johns Hopkins School of Medicine

GOMOLL, Andreas, M.D., Hospital for Special Surgery

GRANDE, Daniel, Ph.D., Feinstein Institutes for Medical Research

GUILAK, Farshid, Ph.D., Washington University

HOCHBERG, Marc, M.D., M.P.H., University of Maryland

HUARD, Johnny, Ph.D., Steadman Philippon Research Institute

LAPTEVA, Larissa, M.D., M.H.S., M.B.A., U.S. Food and Drug Administration

LATTERMANN, Christian, M.D., Brigham and Women’s Hospital

LEONG, Amye, M.B.A., Healthy Motivation

LUTZKO, Carolyn, Ph.D., Cincinnati Children’s Hospital

MONT, Michael, M.D., Sinai Hospital of Baltimore, Inc.

MUSCHLER, George, M.D., Cleveland Clinic Foundation

ROBEY, Pamela, Ph.D., National Institute of Dental and Craniofacial Research

RODEO, Scott, M.D., Hospital for Special Surgery (co-chair)

SARIS, Daniël, M.D., Ph.D., Mayo Clinic College of Medicine

SHAPIRO, Shane, M.D., Mayo Clinic

WHITE, Daniel, P.T., Sc.D., M.Sc., University of Delaware