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"
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).
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.
NIAMS Roundtable on Cartilage Preservation and Restoration in Knee Osteoarthritis (OA) DRAFT Agenda
September 22, 2022
Evidence, Challenges, Gaps, and Opportunities
|Welcome and introductions||Dr. Lindsey Criswell, Dr. Robert Carter|
|11:25-11:35||Patients’ perspectives in OA management||Ms. Amye Leong|
|11:35-12:00||Blood derived orthobiologic therapies for OA||Dr. Constance Chu|
|12:00-12:25||Stem-cell based cell therapies for OA||Dr. Scott Rodeo|
|12:25-12:50||Cartilage regeneration by chondrogenic small molecule drugs||Dr. Marc Hochberg|
12:50 - 1:20 PM – Group Photo and Lunch Break
|1:20-1:45||Matrix-based therapies and tissue-engineered cartilage||Dr. Daniel Grande|
|1:45-2:10||Therapeutic potentials of exosomes in OA||Dr. Daniël Saris|
|2:10-2:35||Gene therapy and gene-editing approaches for OA||Dr. Farshid Guilak|
|2:35-3:00||Limitations and challenges in clinical use of biologics in orthopaedic treatment for OA||Dr. Frank Barry|
3:00 - 3:15 PM – Break
|3:15-3:40||Regulatory considerations for products intended to treat knee osteoarthritis||Dr. Larissa Lapteva|
|5:20-5:30||Closing thoughts||Dr. Lindsey Criswell, Dr. Robert Carter|
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