Contributed Commentary by Steve O’Keeffe, Founder of Angry@Arthritis

November 17, 2023 | Organ regeneration is not a new idea. After creating humans and giving us knowledge, Prometheus was doomed to regenerate his own liver every day to feed Zeus’ pernicious eagle. Osteoarthritis (OA) predates Prometheus; paleontologists have dug up dinosaurs with bad hips.  

Today there are about 32.5 million Americans—including me—who suffer with OA, and the disease is as expensive as it is personally debilitating and depressing. Each year, OA drives $65.5B in U.S. healthcare costs, and cripples U.S. GDP to the tune of $136B, a portion of which is tied to opioid-based pain management. 

The good news is the Federal government is injecting a purported $1B in OA funding. Announced in May of this year and driven out of the Advanced Research Projects Agency for Health (ARPA-H), the Novel Innovations for Tissue Regeneration in Osteoarthritis (NITRO) program has fired up the OA research community.  

Rightly observing that synovial joints are an elegant fusion of bone and articular cartilage, NITRO wants to regenerate both. Significantly, NITRO’s not just looking to stop OA where any cartilage still exists in the joint. ARPA-H wants research teams to fully recover joints, returning them to their pre-disease healthy state. ARPA-H is challenging the OA science community to deliver cures in just 5 years.  

ARPA-H has established three courses to a cure: One, regenerating bone via an interarticular injection. Two, regenerating cartilage, either via an interarticular injection or via an intravenous treatment to cure patients with OA in multiple joints. Three, creating organic, bioreabsorable knee joint replacement so that we no longer need to put metal and plastic prosthetics into our bodies. 

According to ARPA-H, each year Americans get 2.5 million joint replacements. NITRO rightly points out those artificial joints are a flawed fix. Many knee and hip replacements fail. Even the successful ones limit your function post-surgery, which makes running and jumping a very bad idea. And artificial joints only last about 10-20 years, which is why they are not recommended for anyone younger than 60 or 70. Last, but certainly not least, joint replacements only offer viable options for hips and knees. There is nothing for elbows, ankles, feet, hands, and our other myriad articulated joints.  

But the challenge ahead is notoriously complex. Pharma has largely run away from trying to find an OA fix. Novartis is the only major player still in the hunt. Why? Because OA isn’t one disease; it’s a hydra. Different patient populations get it differently. Variables including gender, joint, age, and ethnicity create a smorgasbord of disease subcategories, or phenotypes. That means that treatments that may work for certain slices of the patient population may not work for others.  

If that’s not complex enough, the OA treatment developer community is very siloed. Developers, clinicians, investors, and patients have limited visibility of the existing treatments in clinical trials, and of failed and inactive cures. (That’s why my group, Angry@Arthritis, created the “OA Fix: Trials in the Mix,” the first global OA clinical trial locator and pan-industry resource to help patients navigate the complex OA cure circus.)  

Against that backdrop, we’ll see who won NITRO awards. Researchers were required to create teams to bid on the program to smash the silos that limit powerful collaboration. That likely ruined vacations and weekends across the research community—but, if that pressure creates diamonds, everybody will cheer. ARPA-H’s disruptive approach doesn’t end with the contract awards; it’s driving competition pre- and post-award.  

There’s a lot of great work in the OA space that predates NITRO. I’d like to see 10% of the total NITRO program budget used to accelerate the most promising existing treatments through their trials to see if any of them work. 

More than 32 million American OA sufferers and hundreds of millions more worldwide would be cheering NITRO like crazy, if only they knew about the program. Don’t beat yourself up if you missed it. For some reason, ARPA-H executed a stealth launch in May, so too many folks are still in the dark. The program office also sent out confusing messages about the potential for international leaders to bid on NITRO, which has curtailed many leaders’ participation. 

Prometheus provides fitting inspiration for regeneration as well as enlightenment. Let’s bring this promising NITRO program into the light—and fire up OA regeneration innovation.   

Steve O’Keeffe is the founder of Angry@Arthritis (www.angryatarthritis.org), a 501(c)(3)non-profit organization focused on eliminating osteoarthritis. Angry@Arthritis provides information on new OA cures in development; funds research to these emerging treatments; and advocates for OA to the US Congress. An OA patient and retired entrepreneur, O’Keeffe founded a series of tech companies. A former journalist, he has testified before Congress on technology, government, and workforce issues. He can be reached at sokeeffe@angryarthritis.org .