What is A2M (Alpha 2 Macroglobulin)?

This past few months I’ve been pinged quite a bit on A2M. So what is A2M and why should you care? Is this a next generation treatment for arthritis or is the cart before the horse?

There’s a commercial machine on the market to concentrate this substance from blood and the sales reps that sell orthopedic devices are gearing up to sell these machines to doctors. A2M stands for Alpha 2 Macroglobulin, a naturally occurring protein found in blood plasma. It acts as an inhibitor of a wide variety of proteinases, which are enzymes that break down proteins. In particular, it’s A2M’s ability to inhibit the action of Matrix Metalloproteinases (MMPs) that may make it useful as a possible treatment for arthritis. One type of MMP breaks down the collagen that makes up cartilage and is believed responsible for how arthritis can chew up cartilage in a joint. Hence a naturally occurring protein that blocks the action of this and other MMPs would be potentially a good thing.

How much research do we have that A2M is helpful for arthritis? In a search of the U.S. National Library of Medicine we have 47 articles under the search “alpha 2 macroglobulin osteoarthritis” at this point. Is that a lot? Well as of today’s date we have 501 on mesenchymal stem cells and osteoarthritis. In addition, we have no human clinical trials at all on A2M used in real patients with arthritis. What we do have is a smattering of animal studies and other research looking at samples taken from knee arthritis patients who were never treated with A2M. In contrast, as of last year, we had research on more than 5,000 orthopedic patients treated with bone marrow mesenchymal stem cells. We also have thousands treated with platelet rich plasma (PRP) for various orthopedic problems.

The upshot? Is A2M a next generation arthritis treatment? Well, at this point the concept looks promising, but we have no earthly clue whether this stuff will help real patients. Even if we did have a small clinical study, we’d have to also have a trial comparing it to the much better tested stem cells or platelet rich plasma, as we have multiple studies showing that this seems to help arthritis patients. Last year we tested our procedures with A2M assays and they all contain the protein, but we’ve been unable to identify how much of this stuff you would need to have a clinical effect, which is largely because nobody knows. I also expect that most PRP procedures being done today also contain A2M. So only the next decade will tell if A2M is worth concentrating and if that beats commonly used PRP shots in any way. In the meantime we’ll wait a bit to see how it all pans out.

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Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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