From the Guidelines
Alpha-2-macroglobulin (A2M) has been found to have potential benefits in reducing musculoskeletal morbidity in dialysis patients, particularly in slowing the progression of disease when used with non-cuprophane membranes 1. The benefits of A2M are primarily related to its ability to inhibit proteases and reduce inflammation, which can help protect joint health and slow cartilage degradation. Some of the key benefits of A2M include:
- Reducing cartilage breakdown by inhibiting destructive enzymes like matrix metalloproteinases (MMPs) that contribute to osteoarthritis
- Modulating inflammatory responses throughout the body by binding to cytokines and growth factors
- Serving as a carrier protein for various growth factors, potentially supporting tissue repair and regeneration processes However, it's essential to note that the current evidence on A2M is limited, and more research is needed to fully understand its benefits and potential applications. In clinical practice, A2M injections may be used as a treatment for osteoarthritis and other joint conditions, but the use of noncellulosic membranes for dialysis patients with a life expectancy greater than 2 years may be recommended to slow the progression of A2M-related disease 1. Key considerations for the use of A2M include:
- The lack of conclusive data supporting the use of noncellulosic membranes or peritoneal dialysis for A2M-related disease
- The need for continued research into membranes or dialysis techniques that remove more 2-microglobulin
- The potential benefits of A2M in reducing musculoskeletal morbidity in dialysis patients, particularly when used with non-cuprophane membranes 1.
From the Research
Benefits of Alpha-2 Macroglobulin (A2M)
- A2M has many diversified and complex functions, including the ability to inhibit a broad spectrum of proteases without the direct blockage of the protease active site 2
- A2M is involved in the regulation, transport, and a host of other functions, such as regulating binding of transferrin to its surface receptor, binding defensin and myelin basic protein, and binding several important cytokines, including basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), nerve growth factor (NGF), interleukin-1β (IL-1β), and interleukin-6 (IL-6) 2
- A2M can stabilise and facilitate the clearance of the Alzheimer's disease-associated amyloid beta (Aβ) peptide 3
- A2M can influence the signalling of cytokines and growth factors, including neurotrophins 3
- A2M has emerged as a unique potential treatment of cartilage-based pathology and inflammatory arthritides, with autologous concentrated A2M from plasma being used to successfully treat various painful arthritides 4
- A2M has been implicated biochemically in binding and degradation of the amyloid beta (Abeta) protein, which accumulates in senile plaques in Alzheimer's disease 5, 6
- A2M may participate in a common disease pathway with other proteins, including apolipoprotein E and the amyloid precursor protein, which have each been genetically linked to Alzheimer's disease 6
Potential Therapeutic Applications
- A2M may be used as a biomarker for the diagnosis and prognosis of a number of diseases, including Alzheimer's disease 2, 5, 6
- A2M may be used to treat cartilage-based pathology and inflammatory arthritides, with future directions focusing on recombinant variants that enhance its anti-inflammatory and disease-modifying potential 4