Sprifermin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-Related Diseases

Abstract

When suffering from osteoarthritis (OA), articular cartilage homeostasis is out of balance and the living quality declines. The treatment of knee OA has always been an unsolved problem in the world. At present, symptomatic treatment is mainly adopted for OA. Drug therapy is mainly used to relieve pain symptoms, but often accompanied with adverse reactions; surgical treatment involves the problem of poor integration between the repaired or transplanted tissues and the natural cartilage, leading to the failure of repair. Biotherapy which aims to promote cartilage in situ regeneration and to restore endochondral homeostasis is expected to be an effective method for the prevention and treatment of OA. Disease-modifying osteoarthritis drugs (DMOADs) are intended for targeted treatment of OA. The DMOADs prevent excessive destruction of articular cartilage through anti-catabolism and stimulate tissue regeneration via excitoanabolic effects. Sprifermin (recombinant human FGF18, rhFGF18) is an effective DMOAD, which can not only promote the proliferation of articular chondrocyte and the synthesis of extracellular matrix, increase the thickness of cartilage in a dose-dependent manner, but also inhibit the activity of proteolytic enzymes and remarkedly slow down the degeneration of cartilage. This paper reviews the unique advantages of Sprifermin in repairing cartilage injury and improving cartilage homeostasis, aiming to provide an important strategy for the effective prevention and treatment of cartilage injury-related diseases.

Intra-articular Injections for Treating Knee Osteoarthritis: A Classification According to Their Mechanism of Action

“…Sprifermin is a drug that belongs to the fibroblast growth factor (FGF) family; it is the recombinant form of human FGF 18, and it is considered a disease-modifying drug for osteoarthritis with anabolic properties on articular cartilage. 3,13 The mechanism of action of sprifermin is exerted through the activation of FGF receptor 3 on the surface of the chondrocyte; it promotes the proliferation of chondrocytes, synthesis of extracellular matrix, and the increase in cartilage thickness. Sprifermin also inhibits the activity of proteolytic enzymes such as MMP-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5, and significantly reduces the degeneration of articular cartilage.…”

“…2,3 Standard IAIs used to treat KOA include CSs and HA. 4,5 In recent years, however, other options have been proposed for treating KOA through IAI, including ozone, 6 platelet-rich plasma (PRP), 7 botulinum toxin type A (BTA), 8 prolotherapy with hypertonic dextrose (PHD), 9 mesenchymal stem cells, 10 TissueGene-C (allogeneic chondrocytes modified to overexpress transforming growth factor-β1 [TGF-β1]), 11 as well as disease-modifying drugs such as lorecivivint 12 or sprifermin, 13 reporting beneficial effects; however, none of them are currently a standard treatment for the management of KOA.…”

Sprifermin for Treatment of Osteoarthritis: Recombinant Fibroblast Growth Factor 18 as a Possible Disease-Modifying Knee Osteoarthritis Drug

“…Based on encouraging results from preclinical studies and clinical trials in patients, sprifermin has come into focus as a promising DMOAD candidate [56][57][58]. Sprifermin, also known as recombinant human fibroblast growth factor 18 (rhFGF18), is a truncated 170-amino acid form of FGF18, from which the signal sequence, and the eleven C-terminal amino acids have been removed [59].…”

“…Sprifermin is currently the only potential FGF-based DMOAD that has been used in clinical trials for knee OA [56][57][58]. Five RCTs have yet been initiated -sponsored by Merck KGaA/ EMD Serono (Darmstadt, Germany), two were terminated due to low recruitment.…”

Formononetin improves the inflammatory response and bone destruction in knee joint lesions by regulating the NF‐kB and MAPK signaling pathways

“…At present, the widely used drugs focus on relieving joint pain, such as disease‐relieving OA drugs (DMOADs), but they do not have a good ability to relieve the disease itself (Song et al, 2021). More importantly, most patients are in the early stage of knee injury or OA, and OA is also the main reason for knee arthroplasty in the late stage of the disease (Kwon et al, 2019; Song et al, 2021). Therefore, we need to study and discuss how to alleviate the pain caused by the disease and effectively treat the disease itself.…”