Receptor antibodies as novel therapeutics for diabetes

doi:10.1126/scitranslmed.3003447

Comment

. 2011 Dec 14;3(113):113ps47.

doi: 10.1126/scitranslmed.3003447.

Receptor antibodies as novel therapeutics for diabetes

Siegfried Ussar¹, Sara G Vienberg, C Ronald Kahn

Affiliations

PMID: 22174312
PMCID: PMC4374142
DOI: 10.1126/scitranslmed.3003447

Comment

Receptor antibodies as novel therapeutics for diabetes

Siegfried Ussar et al. Sci Transl Med. 2011.

. 2011 Dec 14;3(113):113ps47.

doi: 10.1126/scitranslmed.3003447.

Authors

Siegfried Ussar¹, Sara G Vienberg, C Ronald Kahn

Affiliation

¹ Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA.

PMID: 22174312
PMCID: PMC4374142
DOI: 10.1126/scitranslmed.3003447

Abstract

Antibodies to receptors can block or mimic hormone action. Taking advantage of receptor isoforms, co-receptors, and other receptor modulating proteins, antibodies and other designer ligands can enhance tissue specificity and provide new approaches to the therapy of diabetes and other diseases.

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Figures

**Figure 1. Mechanisms of stimulatory antibodies**
Antibodies can enhance receptor signaling in multiple ways. Antibodies can promote ligand independent receptor dimerization and activation and thereby circumvent limitations of ligand stability and production. Tissue specific receptor activation can be achieved by targeting receptor/ co-receptor complexes, or individual receptor splice variants. In addition, circulating modulatory protein/ receptor complexes provide a tempting target to incorporate paracrine signals into receptor activation. Finally ligand induced receptor activation can be fine tuned using allosteric antibodies.

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Comment on

Amelioration of type 2 diabetes by antibody-mediated activation of fibroblast growth factor receptor 1.
Wu AL, Kolumam G, Stawicki S, Chen Y, Li J, Zavala-Solorio J, Phamluong K, Feng B, Li L, Marsters S, Kates L, van Bruggen N, Leabman M, Wong A, West D, Stern H, Luis E, Kim HS, Yansura D, Peterson AS, Filvaroff E, Wu Y, Sonoda J. Wu AL, et al. Sci Transl Med. 2011 Dec 14;3(113):113ra126. doi: 10.1126/scitranslmed.3002669. Sci Transl Med. 2011. PMID: 22174314

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References

1. Wu A, Kolumam G. Amelioration of Type 2 Diabetes by Antibody-mediated Activation of Fibroblast Growth Factor Receptor 1. 2011 (to be completed by editor) - PubMed
1. Michalek K, Morshed SA, Latif R, Davies TF. TSH receptor autoantibodies. Autoimmun.Rev. 2009;9:113–116. - PMC - PubMed
1. Flier JS, Kahn CR, Roth J. Receptors, antireceptor antibodies and the mechanism of insulin resistance. N.Engl.J.Med. 1979;300:413–419. - PubMed
1. Lang B, Vincent A. Autoimmune disorders of the neuromuscular junction. Curr.Opin.Pharmacol. 2009;9:336–340. - PubMed
1. Kliewer SA, Mangelsdorf DJ. Fibroblast growth factor 21: from pharmacology to physiology. Am.J.Clin.Nutr. 2010;91:254S–257S. - PMC - PubMed

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[1] Wu A, Kolumam G. Amelioration of Type 2 Diabetes by Antibody-mediated Activation of Fibroblast Growth Factor Receptor 1. 2011 (to be completed by editor) - PubMed

[2] Wu A, Kolumam G. Amelioration of Type 2 Diabetes by Antibody-mediated Activation of Fibroblast Growth Factor Receptor 1. 2011 (to be completed by editor) - PubMed

[3] Michalek K, Morshed SA, Latif R, Davies TF. TSH receptor autoantibodies. Autoimmun.Rev. 2009;9:113–116. - PMC - PubMed

[4] Michalek K, Morshed SA, Latif R, Davies TF. TSH receptor autoantibodies. Autoimmun.Rev. 2009;9:113–116. - PMC - PubMed

[5] Flier JS, Kahn CR, Roth J. Receptors, antireceptor antibodies and the mechanism of insulin resistance. N.Engl.J.Med. 1979;300:413–419. - PubMed

[6] Flier JS, Kahn CR, Roth J. Receptors, antireceptor antibodies and the mechanism of insulin resistance. N.Engl.J.Med. 1979;300:413–419. - PubMed

[7] Lang B, Vincent A. Autoimmune disorders of the neuromuscular junction. Curr.Opin.Pharmacol. 2009;9:336–340. - PubMed

[8] Lang B, Vincent A. Autoimmune disorders of the neuromuscular junction. Curr.Opin.Pharmacol. 2009;9:336–340. - PubMed

[9] Kliewer SA, Mangelsdorf DJ. Fibroblast growth factor 21: from pharmacology to physiology. Am.J.Clin.Nutr. 2010;91:254S–257S. - PMC - PubMed

[10] Kliewer SA, Mangelsdorf DJ. Fibroblast growth factor 21: from pharmacology to physiology. Am.J.Clin.Nutr. 2010;91:254S–257S. - PMC - PubMed

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Receptor antibodies as novel therapeutics for diabetes

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