Really sad, but interesting MSC trial just failed when placebo was introduced
There's a company in Australia doing iPSC-derived MSCs, if you don't know what that is, could ask ChatGPT, but here's a really quick overview:
You can take an adult cell (skin cell, blood cell, etc.) and reverse it back into a super powerful stem cell, almost as powerful/versatile as an embryonic stem cell, which is able to create every tissue in the body. Doing this in the lab is called an induced pluripotent stem cell, or iPSC. You are inducing (forcing) it to become pluripotent (can turn into many things).
You can take that iPSC and make mesenchymal stem cells, which are used in orthopedics and some other indications like autoimmune stuff etc, and you can make a buttload of them this way without a bone marrow aspiration.
This company, Cynata Therapeutics, just put that to the test in a Phase 3 trial of those iPSC-derived MSCs for knee osteoarthritis, with a placebo arm. It was a big deal for the industry, I think the first company to attempt this (though don't quote me).
Sorta surprisingly, the problem wasn't that the stem cell group didn't report improvement, they actually improved really well. The problem is, the placebo group also reported the same improvement. This, of course, means it failed, and there's something else happening.
The CEO had some interesting remarks about why. His theory is basically that people have seen stuff online about stem cells, there's a huge enthusiasm for them for just about anything, especially orthopedics. So much so, if you tell the patient that's what they're getting, they're likely to report improvement, even if it's just saline. However, it's important to note that iPSC-derived MSCs are very new, and not what is injected in pretty much any CCI situation (yet).
There have been a few attempts at placebo-controlled trials for orthopedic stem cells:
- Mayo Clinic did an interesting study. Patients with bilateral (both knees) knee arthritis received bone marrow-derived MSCs in one knee and saline in the other; both knees improved at about the same rate.
- Duke conducted a study that randomized patients to receive steroids (control), stromal vascular fraction (adipose-derived MSCs), bone marrow-derived MSCs, or umbilical cord tissue, all of which reported about the same improvement.
There are however some positive ones, like Cartistem from Korea, which is MSCs made from umbilical cord blood. They showed great improvement over placebo, and even confirmed cartilage regeneration via biopsy/cameras in the knee iirc. That company just passed its Phase 3 in Japan, and is starting in the US sometime this year; pretty hopeful for them.
There are a handful of others in the pipeline too, so it's not all doom gloom and scams.
But, it does beg an uncomfortable question in CCI... what happens if we did a placebo controlled trial? Truly, what would happen here? We've seen that the stem cell group reportedly shows subjective improvement, based on the PICL app/charts posted on reddit. But, what would a placebo group show? I don't have any insider knowledge, so of course it's just an unanswered question, but I feel it's a very important one. And not just PICL, but the same goes for posteriors or other therapies from any random clinic.
If the data showed most of what the success stories (even my own, gulp) is actually placebo, think about how far the train is from the station. I know many people who have given their retirements, second mortgage on their home, I sold my lovely jeep, etc. already.
There are also a lot of people who can't afford the injections, but are told it's pretty much the only option, and suffer a lot because of that.
That's been on my mind a lot recently, of course I would want to know, and think patients deserve the right to know the answer to that, but it's very awkward to think about.
