Osteoarthritis gene therapy in 2022

Abstract

Purpose of reviewTo assess the present status of gene therapy for osteoarthritis (OA). Recent findingsAn expanding list of cDNAs show therapeutic activity when introduced into the joints of animals with experimental models of OA. In vivo delivery with adenovirus or adeno-associated virus is most commonly used for this purpose. The list of encoded products includes cytokines, cytokine antagonists, enzymes, enzyme inhibitors, growth factors and noncoding RNA. Elements of CRISPR-Cas have also been delivered to mouse knees to ablate key genes. Several human trials have been initiated, using transgenes encoding transforming growth factor-b 1 , interleukin-1 receptor antagonist, interferon-b, the NKX3.2 transcription factor or variant interleukin-10. The first of these, using ex vivo delivery with allogeneic chondrocytes, gained approval in Korea which was subsequently retracted. However, it is undergoing Phase III clinical trials in the United States. The other trials are in Phase I or II. No gene therapy for OA has current marketing approval in any jurisdiction.

Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: A scoping review

“…Of note, approval of TG-C as gene therapy for OA under the name of Invossa was revoked in Korea when it became apparent that the transgenic cells were mainly HEK293 cells instead of chondrocytes, and its status is currently being investigated. In the US, on the other hand, trials are ongoing as HEK293 cells had been used from the beginning [reviewed in ( 64 )].…”

Osteoarthritis 2050 projections and its multiple mitigation challenges

“…In particular, small diverse samples, rather than large scale robust studies that can enable definitive answers to important genetic and epigenetic correlates of osteoarthritis and what should its prevention look like, fail however to often situate the condition in the context of the local overall joint environment and forces acting or failing to act optimally on the joint. 17 Other reported perspectives include genetic based therapies and explanatory factors, [18][19][20] aspects of biomaterial development to treat osteoarthritis, 21,22 such as collagen chondro protection 23,24 and various lubricants 25 but few specifically account for the origin of the disease that is clearly quite diverse, 1 and may include vulnerability to excess stress as well as abnormal stress reactions that might be remediable, but may not be addressed by focal solutions or those that are not actionable or clearly understood. 26 In addition, biological cell based therapies that do not account for the overall environment of the damaged joint are also likely to prove suboptimal at best in clinical terms, no matter how carefully these are construed in the lab or tested on non-human samples.…”

New Horizons in Treatment of Knee Osteoarthritis: A Brief Look-up at Emerging Approaches

“…Several cDNAs have shown therapeutic efficacy, including cytokines, cytokine antagonists, enzymes, and growth factors. Human clinical trials have also set in with six gene therapies in development [216].…”