Polyethylene glycol-conjugated human adrenomedullin as a possible treatment for vascular dementia

Nagata, Sayaka; Yamasaki, Motoo; Kïtamura, Kazuo

doi:10.1016/j.peptides.2019.170133

Cited by 5 publications

(2 citation statements)

References 25 publications

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“…17) Furthermore, daily injections of 80 nmol/kg AM are necessary to treat DSS-induced colitis in mice, but a single injection of 25 nmol/kg 60 kDa PEG-AM improved the same model. 25) PEG-AM is more useful because the dose and frequency of administration are reduced, which improves the QOL.…”

Section: Discussionmentioning

confidence: 99%

Activation of Calcitonin Gene-Related Peptide and Adrenomedullin Receptors by PEGylated Adrenomedullin

Akashi

Nagata

Yamasaki

et al. 2020

Biological & Pharmaceutical Bulletin

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Adrenomedullin (AM) improves colitis in animal models and patients with inflammatory bowel disease. We have developed a PEGylated AM derivative (PEG-AM) for clinical application because AM has a short half-life in the blood. However, modification by addition of polyethylene glycol (PEG) may compromise the function of the original peptide. In this paper, we examined the time course of cAMP accumulation induced by 5 and 60 kDa PEG-AM and compared the activation of calcitonin gene-related peptide (CGRP), AM1 and AM2 receptors by AM, 5 and 60 kDa PEG-AM. We also evaluated the effects of antagonists on the action of 5 and 60 kDa PEG-AM. PEG-AM stimulated cAMP production induced by these receptors; the increase in cAMP levels resulting from application of PEG-AM peaked at 15 min. Moreover, PEG-AM activity was antagonized by CGRP (8-37) or AM (22-52) (antagonists of CGRP and AM receptors, respectively) and the maximal response was not suppressed. These findings indicate that the effects of PEG-AM are similar to those of native AM.

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Section: Discussionmentioning

confidence: 99%

Activation of Calcitonin Gene-Related Peptide and Adrenomedullin Receptors by PEGylated Adrenomedullin

Akashi

Nagata

Yamasaki

et al. 2020

Biological & Pharmaceutical Bulletin

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“…The 60 kDa PEGylated AM has shown therapeutic usefulness in a rodent model of colitis, similar to that of native AM [ 139 ]. Additionally, 60 kDa PEGylated AM was effective in a rat model of vascular dementia [ 142 ]. Long-lasting and subcutaneously injectable formulations of AM will be applied as chronic therapy, such as maintenance therapy for treating patients with IBD.…”

Section: Am Modifications To Extend Its Half-life In the Bloodstreammentioning

confidence: 99%

Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases

Kita

Kïtamura

2022

Hypertens Res

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Adrenomedullin (AM) is a vasodilative peptide with various physiological functions, including the maintenance of vascular tone and endothelial barrier function. AM levels are markedly increased during severe inflammation, such as that associated with sepsis; thus, AM is expected to be a useful clinical marker and therapeutic agent for inflammation. However, as the increase in AM levels in cardiovascular diseases (CVDs) is relatively low compared to that in infectious diseases, the value of AM as a marker of CVDs seems to be less important. Limitations pertaining to the administrative route and short half-life of AM in the bloodstream (<30 min) restrict the therapeutic applications of AM for CVDs. In early human studies, various applications of AM for CVDs were attempted, including for heart failure, myocardial infarction, pulmonary hypertension, and peripheral artery disease; however, none achieved success. We have developed AM as a therapeutic agent for inflammatory bowel disease in which the vasodilatory effect of AM is minimized. A clinical trial evaluating this AM formulation for acute cerebral infarction is ongoing. We have also developed AM derivatives that exhibit a longer half-life and less vasodilative activity. These AM derivatives can be administered by subcutaneous injection at long-term intervals. Accordingly, these derivatives will reduce the inconvenience in use compared to that for native AM and expand the possible applications of AM for treating CVDs. In this review, we present the latest translational status of AM and its derivatives.

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Vascular dementia: A microglia's perspective

Yang

Zhao

Zhu

et al. 2022

Ageing Research Reviews

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Polyethylene glycol-conjugated human adrenomedullin as a possible treatment for vascular dementia

Cited by 5 publications

References 25 publications

Activation of Calcitonin Gene-Related Peptide and Adrenomedullin Receptors by PEGylated Adrenomedullin

Activation of Calcitonin Gene-Related Peptide and Adrenomedullin Receptors by PEGylated Adrenomedullin

Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases

Vascular dementia: A microglia's perspective

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