On the Mechanisms of Action of the Low Molecular Weight Fraction of Commercial Human Serum Albumin in Osteoarthritis

Abstract

: The low molecular weight fraction of commercial human serum albumin (LMWF5A) has been shown to successfully relieve pain and inflammation in severe osteoarthritis of the knee (OAK). LMWF5A contains at least three active components that could account for these antiinflammatory and analgesic effects. : We summarize in vitro experiments in bone marrow–derived mesenchymal stem cells, monocytic cell lines, chondrocytes, peripheral blood mononuclear cells, fibroblast-like synoviocytes, and endothelial cells on the biochemistry of anti-inflammatory changes induced by LMWF5A. We then look at four of the major pathways that cut across cell-type considerations to examine which biochemical reactions are affected by mTOR, COX-2, CD36, and AhR pathways. All three components show anti-inflammatory activities in at least some of the cell types. : The in vitro experiments show that the effects of LMWF5A in chondrocytes and bone marrow– derived stem cells in particular, coupled with recent data from previous clinical trials of single and multiple injections of LMWF5A into OAK patients demonstrated improvements in pain, function, and Patient Global Assessment (PGA), as well as high responder rates that could be attributed to the multiple mechanism of action (MOA) pathways are summarized here. In vitro and in vivo data are highly suggestive of LMWF5A being a disease-modifying drug for OAK.

Identification of TGFβ signatures in six murine models mimicking different osteoarthritis clinical phenotypes

“…Moreover, in chondrocytes from patients with OA, expression of thrombospondin (a CD36 ligand) is strongly decreased concomitantly with the increase in CD36 expression [30]. More recently, the anti-inflammatory and analgesic effects of serum albumin in patients with knee OA was related to inhibition of CD36 in synoviocytes, macrophages and chondrocytes [31]. In addition, our study suggests that CD36 might be a specific biomarker of post-traumatic OA.…”

Serum Albumin as Prognostic Marker for Older Adults in Hospital and Community Settings

“…Low serum albumin is not only indicative of poor nutritional status and inflammation but also serves as a comprehensive marker of an individual’s overall health vulnerability ( Levitt & Levitt, 2017 ; G. Li et al, 2022 ; Singh et al, 2019 ). Its correlation with cardiovascular diseases, acute respiratory distress syndrome, acute stroke, and chronic kidney disease contributes to the observed elevated mortality rates ( Bar-Or et al, 2019 ; G. Li et al, 2022 ). In patients with end-stage renal failure, the association with increased inflammation and decreased nutritional status further heightens mortality risk ( Ndlovu et al, 2019 ; Singh et al, 2019 ).…”

The novel immunomodulatory biologic LMWF5A for pharmacological attenuation of the “cytokine storm” in COVID-19 patients: a hypothesis

“…The low molecular weight fraction of commercial human serum albumin (LMWF5A), a novel biologic drug in development for the treatment of inflammation associated with osteoarthritis, exhibits mechanisms of action that may be complimentary to addressing the innate-immunemediated inflammation seen in patients suffering from COVID-19. In the course of development history, the biologic effects of LMF5A have been established using a variety of human immune cell ex vivo and in vitro models stimulated using the DAMP, TLR4 agonist lipopolysaccharide (LPS) as well as relevant barrier-function assays using human endothelial cells (Table 1; also see review on LMWF5A mechanisms of action [25]). Thus, we hypothesize that LMWF5A could improve the clinical outcomes of COVID-19 by attenuating hyperinflammation and the potential development of a cytokine storm as well as the resulting increase in vascular permeability.…”