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    Home > Active Ingredient News > Study of Nervous System > Cutting-edge information| review the clinical significance of serum albumin, and explore whether FcRn antagonists are "enemies" or "friends" for their homeostasis?

    Cutting-edge information| review the clinical significance of serum albumin, and explore whether FcRn antagonists are "enemies" or "friends" for their homeostasis?

    • Last Update: 2022-09-09
    • Source: Internet
    • Author: User
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    Serum albumin (SA), as the most abundant soluble protein in the body, participates in a variety of regulatory functions and undertakes the binding and transport role




    Clinical significance of SA: it is involved in regulating multiple functions of the human body and jointly maintaining homeostasis in the body


    As we all know, SA, as the most abundant plasma protein in the blood, plays an important role


    √ Endogenous binding and transport: SA plays a leading role in the binding and transport of many endogenous molecules throughout the body, including thyroxine, bilirubin, amino acids, and fatty acids (FAs


    √ Exogenous binding and transport: SA has a strong binding and transporting exogenous molecules, so for drugs entering the human body, SA is the "main force" of binding exogenous drugs


    √ Anti-inflammatory and antioxidant: SA binds to multiple mediators of inflammation and is involved in modulating the immune response



    Consequences of SA concentration imbalance: affect the efficacy and side effects of drugs, which is not conducive to the prognosis of many diseases


    In healthy people, the concentration of SA is at a steady-state level



    Effect of FcRn antagonists on SA: Clinical studies have shown that efgartigimod use does not affect albumin levels


    FcRn is a widely expressed cell receptor that is mainly found in acidic endosomes



    √ In a 34-week Phase II multicenter, open-label feasibility trial, 34 patients with mild to moderate pemphigus vulgaris (PV)/defoliative pemphigus who received efgartigimod were included to explore the efficacy and safety


    √ Finally, the Phase III ADAPT trial of efgartigimod for gMG was a 26-week randomized, double-blind, placebo-controlled, global multicenter clinical study in which 167 adult patients received 10 mg/kg intravenous infusion of efgartigimod and placebo, respectively, to assess the efficacy and safety
    of efgartigimod in the treatment of gMG.

    The study shows that efgartigimod treatment can bring significant and rapid clinical benefits, with good safety and tolerability
    .

    In addition, as in phase I and PHASE II studies, no reduction in SA concentrations was
    observed8.

    From the current data, efgartigimod has almost no effect on SA concentrations in the treatment of many diseases, which may make its efficacy and safety more stable
    .

    Currently, efgartigimod has been approved by the FDA, Japan and the European Union for the treatment of adult gMG patients
    .

    Unlike other FcRn antagonists, efgartigimod is a human IgG1 antibody Fc fragment, a natural ligand
    of FcRn.

    Compared with endogenous IgG, efgartigimod has a stronger
    affinity with FcRn.

    However, it is unclear whether differences in effect on SA concentration may be related to differences in the design of FcRn antagonists, such as structure (full-length IgG vs Fc fragments), subclasses, Fc effector regions, binding patterns, affinity, pH dependence, or binding epitopes
    .

    Expert Profiles


    Professor Bu Bitao

    • Deputy Director of the Department of Neurology, Professor, Chief Physician, Master/Doctoral Supervisor of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Deputy Director of the Institute of Neurology of Tongji Hospital
    • Chairman of the Neurology Branch of Hubei Association of Chinese and Western Integration
    • Member of myopathy group and immunology group of Neurology Branch of Chinese Medical Association
    • Director of The Tongji Center for the Standardized Training of Diagnosis and Treatment of Neuromuscular Diseases and Peripheral Neuropathies in China
    • Standing Committee Member of Neuroimmune Branch of Chinese Stroke Society
    • Member of the Peripheral Neurology Collaborative Group of the Neurology Branch of the Chinese Medical Association
    • Leader of the Immunology Group of the Neurology Branch of Wuhan Medical Association
    • Member of the Standing Committee of the Neurology Branch of Hubei Medical Association
    • Overseas member of the American Society of Neuroscience



    Expert reviews

    Attention to the role of serum albumin in autoimmune neurological diseases

    This review systematically summarizes the physiological role of serum albumin (SA) and the important role
    of neonatal Fc receptors (FcRn) in maintaining SA homeostasis.

    SA plays an important physiological role in the body, such as anti-inflammatory, antioxidant and maintenance of intrahydral homeostasis, while also binding and transporting a variety of endogenous molecules and drug molecules
    .

    This review highlights the relationship between SA concentration imbalance and disease outcome and drug efficacy, so maintaining normal SA concentrations is important
    for the treatment of autoimmune diseases.

    A new generation of drugs, FcRn antagonists, has been developed for clinical use, and efgartigimod has been approved by the FDA for adult gMG treatment and is about to be available
    in China.

    One wonders, what kind of impact does this type of product have on SA? Will it affect the outcome of the disease? This review systematically summarizes the effects of several current common antagonists on SA, including Rozanolixizumab, Nipocalimab, Orilanolimab, Batoclimab, and efgartigimod, providing evidence that efgartigimod has little effect on SA concentrations, while several other antagonists show some degree of effect
    .

    The review reminds clinicians to pay attention to changes in SA concentrations in patients treated with FcRn antagonists, and to further explore the relationship between SA concentration changes and disease outcomes to design safer and more reasonable treatment options
    .

    brief summary

    SA is involved in regulating many functions of the human body and plays an important role
    in maintaining homeostasis in the body.

    Among them, SA bears the role of exogenous drug binding and transport, and sa concentration changes are related to drug efficacy and toxicity and related disease prognosis
    .

    Therefore, understanding the clinical significance of SA and the possible consequences of changes in SA concentrations can help with disease management and drug research
    .

    FcRn antagonists such as Efgartigimod have been shown as innovative drugs in the treatment of IgG-mediated autoimmune diseases such as MG
    .

    However, in the future research and application process, it is necessary to consider the longer-term efficacy and safety issues, the choice of the best treatment plan, as well as the management of some complications and drug-to-drug interactions
    .

    Exploring the effects of FcRn antagonists on SA concentrations may help address these questions
    .

    Based on the current research data, in addition to efgartigimod, most of the other FcRn antagonists in research have a certain effect on
    SA concentration.

    The reasons for this discrepancy and the possible consequences of these effects need to be further explored
    .

    References:

    1.
    Ward ES, et al.
    Front Immunol.
    2022 Jun 1; 13:892534.

    2.
    Weng YY, et al.
    Medicine (Baltimore).
    2016 Sep; 95(39):e5000.

    3.
    Arques S.
    2020 Oct; 69(4):192-200.

    4.
    Pyzik M, et al.
    Front Immunol.
    2019 Jul 10; 10:1540.

    5.
    Ulrichts P, et al.
    J Clin Invest.
    2018 Oct 1; 128(10):4372-4386.

    6.
    Newland AC, et al.
    Am J Hematol.
    2020 Feb; 95(2):178-187.

    7.
    Goebeler M, et al.
    Br J Dermatol.
    2022 Mar; 186(3):429-439.

    8.
    Howard JF Jr, et al.
    Lancet Neurol.
    2021 Jul; 20(7):526-536.

    ZMCNNP20220825006 Expire Date 2023/08/25

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