Guest Column | August 21, 2023

Is Osteoarthritis Cure — ARPA-H NITRO — Rocket Fuel Or TNT?

By Steve O’Keeffe, founder, Angry@Arthritis

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While you don’t need to be a fossil to suffer from arthritis, paleontologists tell us it hobbled our old buddy T-Rex. Anthropologists tell us the first recorded human osteoarthritis (OA) hobbler dates back to 4500 BC. But, today, we’re taking a new look at this ancient affliction. The U.S. federal government just unveiled a moonshot to fix OA. Rumored to be funded at $1 billion and launched out of the new whizz-bang Advanced Research Project Agency for Health (ARPA-H), the Novel Innovations for Tissue Regeneration in Osteoarthritis, or NITRO program, plans to boldly go where no one has gone before — cure OA in five years. As an OA sufferer, my dinosaur OA bones are shaking with excitement.

OA’s Big And Ugly

So, let’s look at the scale and complexity of the disease and perhaps help orient our intrepid NITRO OA astronauts. OA is massive. The disease afflicts more than 32 million Americans and hundreds of millions more folks worldwide. In fact, if we’re lucky to live long enough, 100 percent of us will eventually suffer from OA. It’s painful, it’s expensive, and it’s exploding. According to ARPA-H, each year 2.5 million Americans get joint replacements. OA drives $65.5 billion in U.S. healthcare costs. And according to the U.S. government, the disease drags down our national economic productivity by $136 billion each year, a portion of which is attributable to opioid-based pain management. And, as our population ages and gets heavier, OA is absolutely along for the ride.

One Size Doesn’t Fit All — No Silver Bullet

You get the drift. OA is big. And it’s also far from simple. You see, OA is not one disease. And to be clear, I’m demarcating OA from its sister so-called inflammatory conditions — things like rheumatoid arthritis, psoriatic arthritis, lupus, and the like. OA afflicts different folks differently in different joints at different times in their lives. OA hits in hands, knees, shoulders, hips, elbows, and, in fact, in every articulated joint in the body – and we have a lot of them. It hits women more than men. While not exclusively a disease for the aged, OA hits hardest in older populations. It hits various minority populations harder. These patient subcategories of the disease are called phenotypes, and the OA manifestation and course of the disease is different by subcategory. And so, while we’d love to have one silver bullet, curing OA is not that simple. If it were, we’d surely have slayed this dinosaur years ago.

Pharma Running Scared

In fact, it’s OA’s complexity that has caused so many pharmaceutical companies to run screaming from efforts to cure the disease. The road to an OA cure is in fact littered with the dead bodies of pharma companies that have tried and failed to create an effective DMOAD, or disease modifying osteoarthritis drug. In fact, Swiss Novartis is the only heavyweight left in the ring. It laudably has three contenders in the FDA clinical trial process. A lot of patients are pinning their hopes on Novartis’ catchily named LNA043.


And, drilling down on that complexity, many in the pharma industry point to the overwhelming complexity of the FDA approval process. There’s wide speculation among OA cure hunters that a series of the OA treatments that failed the FDA approval process may actually work – but not against all patient phenotypes. I’d direct your attention to Sprifermin and UBX0101.

What? Let me rewind that tape. Many OA experts believe that OA cures that failed the FDA trials could work  however, they will not deliver success against every class of patient. For example, drugs may cure OA — and regrow cartilage — in younger patients, let’s say those less than 60, but not in older folks. Some drugs may work in women but not in men. Some may work in tall people — but not folks under 5’ 5”. Well, now I’m being silly, but you get the gist.

Combination Lock

So, that cure complexity opens up one more rip in the space time continuum that I’d like to take you through, before we settle back to NITRO – and talk about the government charting the OA cure course from here to infinity. What if, like the treatment for cancer, OA requires a combination cure approach in order to cure OA in specific phenotypes? What if it’s going to take an injection to tamp down inflammation, a surgery to insert new cartilage, and a treatment to eradicate aging or senescent cells? How do we communicate with the FDA to reimagine the clinical trials process to accelerate our path to a cure — and perhaps take existing treatments out of the dunce corner?


Now, with that context, let’s take a harder look at ARPA-H NITRO. You can read the details here, but we’re not all biology nerds, so let me break it down. Unveiled to almost zero fanfare in May of this year – don’t be mad at yourself if you missed it – the new OA cure rocket ship focuses on three categories of cure: 1) regenerating bone with an injection; 2) regenerating cartilage with an injection – and further, delivering a cure for OA in multiple joints via an intravenous drug; and 3) creating organic, bioresorbable joint replacements so that we no longer need to put metal and plastic prosthetics into our bodies — fake joints that limit our activities, are not suitable for younger active folks, and sadly, wear out in 10 to 15 years. And ARPA-H is challenging bidders to do all that in five years.

This Is Beyond Great

“Hubba, hubba,” I hear all of us OA sufferers cheer. What ARPA-H is doing is precisely what we need in so many ways. The Feds are taking aim at a huge disease that affects a massive swath of the U.S. population — and stepping into a private-sector investment desert that has largely been abandoned by pharma. ARPA-H is challenging the scientists to think outside the box — and, critically, the agency is forcing disparate groups to break down silos and collaborate to create new science and intellectual property.

Not So Fast

However, I regret it’s not that simple. ARPA-H hit the OA research and clinical population with its call for proposals in May, brought some of them in for a review of the requirements in mid-June, and is requiring proposal submissions before the end of July. To say that this timeline is aggressive is an understatement — so much so that developers have quietly been calling the program NUTSO, rather than NITRO. ARPA-H is betting on the requirement to play this game in a hurry-up huddle will shock the research and clinical field out of its accretive, failing ways. Sometimes chaos is the best creativity. We hope the Feds have that right; this is far too huge an opportunity to waste. OA cure hunters will not get this kind of funding again soon, especially not if NITRO fails.

Out With The Old

In the rush for new breakthroughs, NITRO seems to be looking past all the existing innovative OA treatments currently struggling in the FDA’s current approval dungeons. We recently released the OA Fix ~ Clinical Trials in the Mix chart, the first consolidated review of promising treatments traveling from the bench to the bedside. Take a close look at the N-TEC offering currently in testing at the University of Basel. That’s some serious Swiss chocolate.

We also mapped the treatments that failed FDA clinical trials that may actually work, as well as those promising treatments that made it out of the lab but are in search of funding to enter the clinical trial process.

These offerings are the product of decades of work from the OA cure hunter community — pharma, universities, and specialized developers. Maybe it would behoove ARPA-H to take a look at these offerings, try to judge their merits, and consider investing even a tiny portion of the total program budget to see if there’s a way to get these contenders across the line. Yes, we want shiny, new, all singing, all dancing cures — what OA patient wouldn’t put down their cane to dance to that? But, at the same time, the agency should consider the value of potentially viable, more terrestrial treatments alongside the interstellar moonshots? Patients want better therapies quickly, and perfection is the enemy of the good. We only have one life to lead.

Rocket Fuel Or TNT?

As the Feds and research scientists engage in their NITRO Red Bull-powered combat gymnastics, we want to say clearly that we’re cheering from the bleachers but caution all of you that it is easy to get caught up in the excitement and lose critical sight of the patient and the existing science. As we search for new whizz-bang cures, we cannot afford to throw out the baby with the bathwater.

32.5 million Americans need to know about NITRO. We all care about this cure. If we bring back the dinosaurs, they’ll be cheering, too.

About The Author:

Steve O’Keeffe is the founder of Angry@Arthritis — — a nonprofit organization focused on eliminating osteoarthritis. Angry@Arthritis provides consumers with direct access to leading science on new OA cures in development, funds research to these emerging treatments, and advocates for OA to Congress. An OA patient and retired entrepreneur, O’Keeffe founded a series of tech companies. A former journalist, he has testified before Congress on tech, government, and workforce issues.