Alpha-2-Macroglobulin
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Osteoarthritis
Osteoarthritis (OA) is a disease process that results in the breakdown of joint cartilage and underlying bone. Symptoms of OA include joint pain, swelling, and stiffness which typically begin gradually. Initially the symptoms will come and go, and after time they will become constant. There are many factors that contribute to development of OA, including genetics, joint injury, and obesity. Current conservative treatment for OA includes nutrition optimization, exercise, medication, and physical therapy. As the degenerative process continues more aggressive treatments include corticosteroid and hyaluronic acid (Synvisc) injections. These injections can provide good but short term relief. Corticosteroids simply decrease pain and inflammation but do not slow or prevent the progression of the degenerative condition. The last resort option is joint replacement, depending on the joint involved. |
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What is A2M?
Alpha-2-macroglobulin* (A2M) is a protein found in blood. This protein inhibits different enzymes. Many of these enzymes are found in the blood. This protein has become an area of interest in the regenerative medicine field with recent studies showing that this A2M protein also inhibits the activity of some ADAMTS enzymes in joints. These particular ADAMTS enzymes play a role in the breakdown of cartilage with arthritis. This protein is found in normal, healthy joints. |
Studies
There have been studies investigating the benefit of A2M in preventing OA. These studies have been done only in animal models up to this point. The researchers typically induce trauma to a rat knee and compare a placebo injection to A2M injection. The A2M treated animals demonstrate a cartilage sparing effect and slowing of the arthritis process.
These findings have some exciting implications. This protein could easily be isolated from the blood and injected into an arthritic knee and allow for slowing of the arthritis process. Theoretically, if the balance of cartilage breakdown and repair swings in the direction of repair by inhibiting the ADAMTS breakdown enzymes, it is possible the arthritis process may even reverse to a certain degree to allow for repair and regeneration of the damaged cartilage.
There have been studies investigating the benefit of A2M in preventing OA. These studies have been done only in animal models up to this point. The researchers typically induce trauma to a rat knee and compare a placebo injection to A2M injection. The A2M treated animals demonstrate a cartilage sparing effect and slowing of the arthritis process.
These findings have some exciting implications. This protein could easily be isolated from the blood and injected into an arthritic knee and allow for slowing of the arthritis process. Theoretically, if the balance of cartilage breakdown and repair swings in the direction of repair by inhibiting the ADAMTS breakdown enzymes, it is possible the arthritis process may even reverse to a certain degree to allow for repair and regeneration of the damaged cartilage.
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When Should It Be Used?
We have the technology to isolate these proteins from blood and inject into arthritic joints at this time. These proteins are blood products so they are not regulated by the FDA. Currently, these procedures are done all across the US by interested patients. The ethical question involved with this procedure, as with many regenerative medicine options, is whether or not we should recommend these interventions without large human trials to support their use. We know injecting blood products is safe and no harm will be done. We unfortunately don’t know which patients would benefit most from A2M, how often to use it, how much to use, and other details. We will need further investigation to have these specific answers. Until then it is available to those who would like to try this new and experimental option. |
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*These HCT/P (human cells, tissues, and cellular and tissue-based product) used are minimally manipulated, for homologous use only, not combined with another article, and without a systemic effect. This meets the criteria for regulation under section 361 of PHS Act and 21 CFR Part 1271.