What is A2M?

In the United States, around 25 million people are treated for arthritis each year. In addition, the American healthcare system bills millions of dollars for knee pain, back pain, post-traumatic osteoarthritis, and other joint conditions. An exciting cutting-edge treatment in orthopedic medicine is alpha-2-macroglobulin (A2M) injections.

Alpha-2-macroglobulin is a powerful inhibitor of cartilage catabolism and progression of arthritis. In addition, A2M can prevent cartilage breakdown and loss of chondrocytes. Using breakthrough molecular technology, scientists can obtain and concentrate Alpha-2-macroglobulin in your blood, and then concentrate it into a solution that is installed into the joint space.


Osteoarthritis and A2M Therapy

Recent studies have proved that intra-articular A2M supplementation inhibits the progression of osteoarthritis (OA) by protecting the cartilage from persistent inflammation and catabolic factors. A2M therapy is a way to use natural healing proven by science to protect the joints from OA while promoting tissue growth and supporting regeneration and restoration of the affected joint.

Alpha-2-macroglobulin is found naturally in the blood. This substance binds and captures “bad” chemicals in the joint and neutralizes their degenerative abilities. Arthritis joints make many chemicals that destroy the cartilage over time. Called catabolic proteases, these chemicals degrade cartilage and damage the joints by breaking down cartilage cells. Injections of A2M can help prevent this cartilage wasting, which will stop OA disease progression and reduce pain.


Effectiveness of Alpha-2-Macroglobulin

A2M is a broad-spectrum multi-purpose protease inhibitor with a “bait and trap” mechanism. This mechanism captures and inactivates the proteases (chemicals) which damage the joints. Once these chemicals are trapped by A2M, the body gets rid of them through natural mechanisms. A2M has been proven effective in a few studies, but because it is such a new therapy, much more research is needed.

In a study involving 40 people with discogenic (intervertebral disc-related) pain, injections of A2M were given via discography. During the procedure, patients with FACT-positive assays were more likely to show improvement in pain scores and mobility at the follow-up. The success rate as 77% and A2M has determined an efficacious biologic treatment for disco-genic pain.


Alpha-2-Macroglobulin Therapeutic Potential

A2M is found in high concentrations in the blood. There are three proteins in the blood that break down cartilage, and A2M can inhibit all of these substances. The protective characteristics of A2M make it a useful treatment for osteoarthritis, rheumatoid arthritis, disco-genic spine pain, degenerative disc disease, and other cartilage-related conditions. Based on scientific research, concentrated A2M has been identified as a primary therapeutic agent. Additionally, this therapy can actually prevent further joint destruction when used as a preventative treatment.


While A2M therapy is not yet covered by health insurance plans, it is a true biologic treatment that addresses the actual destruction problem. While many treatments are used to ease pain and suffering, A2M injections prevent further joint deterioration by supporting collagen and removing damaging proteins. The FDA has approved the clinical trials involving A2M.

A2M Research Continues

A team of researchers at Cytonics led by Dr. Scuderi built a system that concentrates alpha-2-macroglobulin and platelets. This system removes most platelets, problem proteins, red cells, and white cells. All that is left in the solution is the purified A2M, which is injected in a super-concentrated form into joints and discs. During Scuderi’s research, more than 200 patients have received autologous treatment using A2M.


Many orthopedic specialists are using A2M therapy for treatment of orthopedic problems. In a mini case series study, six patients were treated by doctors who were also candidates for knee replacement surgery. After A2M therapy, five of those were satisfied with the therapy and did not have surgery.


Abrams GD, Safran MR, Shapiro LM, et al. (20140. Fibronectin-aggrecan complex as a marker for cartilage degradation in non-arthritic hips. Knee Surg Sports Traumatol Arthrosc, 22(4):768.
Montesano PX, Cuellar JM, Scuderi GJ (2017). Intradiscal Injection of an Autologous Alpha-2Macroglobulin (A2M) Concentrate Alleviates Back Pain in FAC-Positive Patients. Ortho & Rheum, 4(2).
Scuderi GJ, Golish SR, Cook FF, Cuellar JM, et al. (2011). Identification of a novel fibronectin-aggrecan complex in the synovial fluid of knees with painful meniscal injury. J Bone Joint Surg Am, 93(4):336-340.
Wang, S., Wei, X., Zhou, J., Zhang, J., et. al. Identification of α2-Macroglobulin as a Master Inhibitor of Cartilage-Degrading Factors that Attenuates the Progression of Posttraumatic Osteoarthritis. Arthritis & Rheumatology 66.7 (2014): 1843-1853.