Inhibition of the Wnt Pathway: Potential Benefits for Osteoarthritis

Allan Gibofsky, MD, co-director of the Clinic for Inflammatory Arthritis at the Hospital for Special Surgery, and Professor of Medicine at Weill Cornell Medicine in New York City, discusses inhibition of the Wnt pathway and its potential benefits for the treatment of osteoarthritis. 

A transcript of this interview is available below.

Video transcript

Hello, I’m Allan Gibofsky, Co-director of the Clinic for Inflammatory Arthritis at the Hospital for Special Surgery, and Professor of Medicine at Weill Cornell Medicine in New York City. I’d like to spend a few minutes with you today talking about our work on inhibition of the Wnt pathway and its potential benefits for the treatment of osteoarthritis [recently presented at ACR 2017].¹

Fundamentally, we took a group of patients who had moderate to severe rheumatoid arthritis, those who are known as Kellgren-Lawrence (KL) grade 2 and 3, and gave them a single injection of a novel molecule that was designed to inhibit the Wnt pathway. The Wnt pathway is a series of signaling molecules that are involved in various growth aspects of bone, and it is thought that activation of the Wnt pathway may be important in the resulting degeneration of cartilage and bone that’s seen in osteoarthritis. 

Now osteoarthritis is of course one of the most prevalent musculoskeletal conditions in the United States and the rest of the world, thought to be the result of wear and tear, but there is also a significant inflammatory component in many patients as well.

Consequently, if one can find a way of inhibiting the mechanism that leads to cartilage and bone destruction, one would actually have a way of providing disease modification rather than just symptom modification.

So this was an early investigational study of a dose of a drug called a Wnt inhibitor designed to inhibit the Wnt pathway, which is a series of protein signaling mechanisms in the joint that regulate various aspects of bone growth and bone metabolism. 

We gave 1 intra-articular injection to patients who had moderate to severe osteoarthritis, what’s known as Kellgren-Lawrence grade 2 or 3, which is a standard measure of osteoarthritis clinical severity, and we measured a variety of functional outcomes that are standardized as well. And we found in a small number of patients in this proof of concept study that there was a modest effect on reduction in pain, improvement in function, and also in the techniques used, some early and modest improvement in cartilage as well.

So if one can in fact see improvements in pain, function, and improvements in cartilage growth, one then in essence is aiming for and achieving disease modification rather than just symptom treatment.

Again, I want to significantly point out that this is an early study — it’s a proof of concept study, there were small numbers of patients — yet it is encouraging in that the results of this study will allow us to go forward and treat more patients with this very significant and very disabling disease, which is a major public health problem in the United States and around the rest of the world as well. 

Reference

1. Yazici Y, McAlindon TE, Gibofsky A, Lane NE, Clauw DJ, Armas E, Skrepnik N, Swearingen CJ, DiFrancesco A, Tambiah J, Hochberg M. Results from a 52 Week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/results-from-a-52-week-randomized-double-blind-placebo-controlled-phase-2-study-of-a-novel-intra-articular-wnt-pathway-inhibitor-sm04690-for-the-treatment-of-knee-osteoarthritis/. Accessed December 8, 2017.