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3. Human IAPP is a contributor to painful diabetic peripheral neuropathy

Author

Albariqi, Mohammed M.H., Versteeg, Sabine, Brakkee, Elisabeth M., Coert, J. Henk, Elenbaas, Barend O.W., Prado, Judith, Hack, C. Erik, Hoppener, Jo W.M., and Eijkelkamp, Niels

Subjects
Diagnosis, Complications and side effects, Analysis, Pancreatic beta cells -- Analysis, Diabetes mellitus -- Diagnosis -- Complications and side effects, Diabetes -- Diagnosis -- Complications and side effects
Abstract

Introduction Diabetes mellitus (DM) is a metabolic disorder that affects around 463 million individuals globally (1). DM is one of the most significant worldwide health issues, diminishing quality of life [...], Peripheral neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM). We investigated whether human islet amyloid polypeptide (hIAPP), which forms pathogenic aggregates that damage pancreatic islet [beta] cells in T2DM, is involved in T2DM-associated peripheral neuropathy. In vitro, hIAPP incubation with sensory neurons reduced neurite outgrowth and increased levels of mitochondrial reactive oxygen species. hIAPP-transgenic mice, which have elevated plasma hIAPP levels without hyperglycemia, developed peripheral neuropathy as evidenced by pain-associated behavior and reduced intraepidermal nerve fiber (IENF) density. Similarly, hIAPP Ob/Ob mice, which have hyperglycemia in combination with elevated plasma hIAPP levels, had signs of neuropathy, although more aggravated. In wild-type mice, intraplantar and intravenous hIAPP injections induced long-lasting allodynia and decreased IENF density. Non-aggregating murine IAPP, mutated hIAPP (pramlintide), or hIAPP with pharmacologically inhibited aggregation did not induce these effects. T2DM patients had reduced IENF density and more hIAPP oligomers in the skin compared with non-T2DM controls. Thus, we provide evidence that hIAPP aggregation is neurotoxic and mediates peripheral neuropathy in mice. The increased abundance of hIAPP aggregates in the skin of T2DM patients supports the notion that hIAPP is a potential contributor to T2DM neuropathy in humans.

Published
2023
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5. Human IAPP is a contributor to painful diabetic peripheral neuropathy

Author

CTI Eijkelkamp, Zorgeenheid Plastische Chirurgie Medisch, Brain, Cancer, Infection & Immunity, CTI, CMM Groep Burgering, Child Health, Albariqi, Mohammed Mh, Versteeg, Sabine, Brakkee, Elisabeth M, Coert, J Henk, Elenbaas, Barend Ow, Prado, Judith, Hack, C Erik, Höppener, Jo Wm, Eijkelkamp, Niels, CTI Eijkelkamp, Zorgeenheid Plastische Chirurgie Medisch, Brain, Cancer, Infection & Immunity, CTI, CMM Groep Burgering, Child Health, Albariqi, Mohammed Mh, Versteeg, Sabine, Brakkee, Elisabeth M, Coert, J Henk, Elenbaas, Barend Ow, Prado, Judith, Hack, C Erik, Höppener, Jo Wm, and Eijkelkamp, Niels

Published
2023

8. Macrophages transfer mitochondria to sensory neurons to resolve inflammatory pain

Author

CTI Eijkelkamp, CTI Van der Vlist, Infection & Immunity, Pathologie Opleiding, Cancer, Translational Neuroscience, Brain, Regenerative Medicine and Stem Cells, CTI, Child Health, van der Vlist, Michiel, Raoof, Ramin, Willemen, Hanneke L.D.M., Prado, Judith, Versteeg, Sabine, Martin Gil, Christian, Vos, Martijn, Lokhorst, Roeland E., Pasterkamp, R. Jeroen, Kojima, Toshiyuki, Karasuyama, Hajime, Khoury-Hanold, William, Meyaard, Linde, Eijkelkamp, Niels, CTI Eijkelkamp, CTI Van der Vlist, Infection & Immunity, Pathologie Opleiding, Cancer, Translational Neuroscience, Brain, Regenerative Medicine and Stem Cells, CTI, Child Health, van der Vlist, Michiel, Raoof, Ramin, Willemen, Hanneke L.D.M., Prado, Judith, Versteeg, Sabine, Martin Gil, Christian, Vos, Martijn, Lokhorst, Roeland E., Pasterkamp, R. Jeroen, Kojima, Toshiyuki, Karasuyama, Hajime, Khoury-Hanold, William, Meyaard, Linde, and Eijkelkamp, Niels

Published
2022

11. Dorsal Root Ganglia Macrophages Maintain Osteoarthritis Pain

Author

Raoof, Ramin, primary, Martin Gil, Christian, additional, Lafeber, Floris P.J.G., additional, de Visser, Huub, additional, Prado, Judith, additional, Versteeg, Sabine, additional, Pascha, Mirte N., additional, Heinemans, Anne L.P., additional, Adolfs, Youri, additional, Pasterkamp, R. Jeroen, additional, Wood, John N., additional, Mastbergen, Simon C., additional, and Eijkelkamp, Niels, additional

Published
2021
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12. Cytokine receptor clustering in sensory neurons with an engineered cytokine fusion protein triggers unique pain resolution pathways

Author

IRAS OH Toxicology, dIRAS RA-1, Prado, Judith, Westerink, Remco H S, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Pandit, Aridaman, Versteeg, Sabine, van de Worp, Wouter, Kanters, Deon H A J, Reedquist, Kris A, Koenderman, Leo, Hack, C Erik, Eijkelkamp, Niels, IRAS OH Toxicology, dIRAS RA-1, Prado, Judith, Westerink, Remco H S, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Pandit, Aridaman, Versteeg, Sabine, van de Worp, Wouter, Kanters, Deon H A J, Reedquist, Kris A, Koenderman, Leo, Hack, C Erik, and Eijkelkamp, Niels

Published
2021

13. Dorsal root ganglia macrophages maintain osteoarthritis pain

Author

Infection & Immunity, CTI Eijkelkamp, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, Cancer, TN groep Pasterkamp, Brain, Translational Neuroscience, Child Health, Raoof, Ramin, Gil, Christian Martin, Lafeber, Floris P.J.G., De Visser, Huub, Prado, Judith, Versteeg, Sabine, Pascha, Mirte N., Heinemans, Anne L.P., Adolfs, Youri, Pasterkamp, Jeroen, Wood, John N., Mastbergen, Simon C., Eijkelkamp, Niels, Infection & Immunity, CTI Eijkelkamp, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, Cancer, TN groep Pasterkamp, Brain, Translational Neuroscience, Child Health, Raoof, Ramin, Gil, Christian Martin, Lafeber, Floris P.J.G., De Visser, Huub, Prado, Judith, Versteeg, Sabine, Pascha, Mirte N., Heinemans, Anne L.P., Adolfs, Youri, Pasterkamp, Jeroen, Wood, John N., Mastbergen, Simon C., and Eijkelkamp, Niels

Published
2021

14. Cytokine receptor clustering in sensory neurons with an engineered cytokine fusion protein triggers unique pain resolution pathways

Author

CTI Eijkelkamp, Infection & Immunity, Cancer, Regenerative Medicine and Stem Cells, Lab Reumatologie/Klinische Immunologie, CTI Pandit, Translationele immunologie, Experimentele Afdeling Longziekten, CTI, Brain, Child Health, Prado, Judith, Westerink, Remco H S, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Pandit, Aridaman, Versteeg, Sabine, van de Worp, Wouter, Kanters, Deon H A J, Reedquist, Kris A, Koenderman, Leo, Hack, C Erik, Eijkelkamp, Niels, CTI Eijkelkamp, Infection & Immunity, Cancer, Regenerative Medicine and Stem Cells, Lab Reumatologie/Klinische Immunologie, CTI Pandit, Translationele immunologie, Experimentele Afdeling Longziekten, CTI, Brain, Child Health, Prado, Judith, Westerink, Remco H S, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Pandit, Aridaman, Versteeg, Sabine, van de Worp, Wouter, Kanters, Deon H A J, Reedquist, Kris A, Koenderman, Leo, Hack, C Erik, and Eijkelkamp, Niels

Published
2021

17. Sialic Acid-Engineered IL4-10 Fusion Protein is Bioactive and Rapidly Cleared from the Circulation

Author

CTI Straetemans, CTI Eijkelkamp, Infection & Immunity, Cancer, Apotheek Onderzoek, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, CTI, Child Health, Steen-Louws, Cristine, Boross, Peter, Prado, Judith, Meeldijk, Jan, Langenhorst, Jurgen B, Huitema, Alwin D R, den Hartog, Marcel T, Boon, Louis, Lafeber, Floris P J G, Hack, C Erik, Eijkelkamp, Niels, Popov-Celeketic, Jelena, CTI Straetemans, CTI Eijkelkamp, Infection & Immunity, Cancer, Apotheek Onderzoek, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, CTI, Child Health, Steen-Louws, Cristine, Boross, Peter, Prado, Judith, Meeldijk, Jan, Langenhorst, Jurgen B, Huitema, Alwin D R, den Hartog, Marcel T, Boon, Louis, Lafeber, Floris P J G, Hack, C Erik, Eijkelkamp, Niels, and Popov-Celeketic, Jelena

Published
2019

19. Development of recombinant proteins to treat chronic pain

Author

Prado, Judith, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Raoof, Ramin, Hack, Eric, Eijkelkamp, Niels, Prado, Judith, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Raoof, Ramin, Hack, Eric, and Eijkelkamp, Niels

Published
2018

20. Identification of FAM173B as a protein methyltransferase promoting chronic pain

Author

Willemen, Hanneke L.D.M., Kavelaars, Annemieke, Prado, Judith, Maas, Mirjam, Versteeg, Sabine, Nellissen, Lara J.J., Tromp, Jeshua, Gonzalez Cano, Rafael, Zhou, Wenjun, Jakobsson, Magnus E., Małecki, Jędrzej, Posthuma, George, Habib, Abdella M., Heijnen, Cobi J., Falnes, Pål, Eijkelkamp, Niels, Willemen, Hanneke L.D.M., Kavelaars, Annemieke, Prado, Judith, Maas, Mirjam, Versteeg, Sabine, Nellissen, Lara J.J., Tromp, Jeshua, Gonzalez Cano, Rafael, Zhou, Wenjun, Jakobsson, Magnus E., Małecki, Jędrzej, Posthuma, George, Habib, Abdella M., Heijnen, Cobi J., Falnes, Pål, and Eijkelkamp, Niels

Published
2018

21. Development of recombinant proteins to treat chronic pain

Author

CTI Eijkelkamp, Infection & Immunity, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, Child Health, DDOD, Prado, Judith, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Raoof, Ramin, Hack, Eric, Eijkelkamp, Niels, CTI Eijkelkamp, Infection & Immunity, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, Child Health, DDOD, Prado, Judith, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Raoof, Ramin, Hack, Eric, and Eijkelkamp, Niels

Published
2018

22. Identification of FAM173B as a protein methyltransferase promoting chronic pain

Author

DDOD, Infection & Immunity, CTI Eijkelkamp, CMM Centr. voor Elektr. Microscopie, Cancer, Regenerative Medicine and Stem Cells, Child Health, Willemen, Hanneke L.D.M., Kavelaars, Annemieke, Prado, Judith, Maas, Mirjam, Versteeg, Sabine, Nellissen, Lara J.J., Tromp, Jeshua, Gonzalez Cano, Rafael, Zhou, Wenjun, Jakobsson, Magnus E., Małecki, Jędrzej, Posthuma, George, Habib, Abdella M., Heijnen, Cobi J., Falnes, Pål, Eijkelkamp, Niels, DDOD, Infection & Immunity, CTI Eijkelkamp, CMM Centr. voor Elektr. Microscopie, Cancer, Regenerative Medicine and Stem Cells, Child Health, Willemen, Hanneke L.D.M., Kavelaars, Annemieke, Prado, Judith, Maas, Mirjam, Versteeg, Sabine, Nellissen, Lara J.J., Tromp, Jeshua, Gonzalez Cano, Rafael, Zhou, Wenjun, Jakobsson, Magnus E., Małecki, Jędrzej, Posthuma, George, Habib, Abdella M., Heijnen, Cobi J., Falnes, Pål, and Eijkelkamp, Niels

Published
2018

23. Identification of FAM173B as a protein methyltransferase promoting chronic pain

Author

Willemen, Hanneke L. D. M., primary, Kavelaars, Annemieke, additional, Prado, Judith, additional, Maas, Mirjam, additional, Versteeg, Sabine, additional, Nellissen, Lara J. J., additional, Tromp, Jeshua, additional, Gonzalez Cano, Rafael, additional, Zhou, Wenjun, additional, Jakobsson, Magnus E., additional, Małecki, Jędrzej, additional, Posthuma, George, additional, Habib, Abdella M., additional, Heijnen, Cobi J., additional, Falnes, Pål Ø., additional, and Eijkelkamp, Niels, additional

Published
2018
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24. Sialic Acid-Engineered IL4–10 Fusion Protein is Bioactive and Rapidly Cleared from the Circulation.

Author

Steen-Louws, Cristine, Boross, Peter, Prado, Judith, Meeldijk, Jan, Langenhorst, Jurgen B., Huitema, Alwin D. R., den Hartog, Marcel T., Boon, Louis, Lafeber, Floris P. J. G., Hack, C. Erik, Eijkelkamp, Niels, and Popov-Celeketic, Jelena

Subjects
SPINAL infusions, CHO cell, INTRAVENOUS injections, CHRONIC pain, GLYCOPROTEINS
Abstract

Purpose: Modulating sialylation of therapeutic glycoproteins may be used to influence their clearance and systemic exposure. We studied the effect of low and high sialylated IL4–10 fusion protein (IL4–10 FP) on in vitro and in vivo bioactivity and evaluated the effect of differential sialylation on pharmacokinetic parameters. Methods: CHO cell lines producing low (IL4–10 FP lowSA) and high sialylated (IL4–10 FP highSA) fusion protein were generated. Bioactivity of the proteins was evaluated in an LPS-stimulated whole blood assay. Pharmacokinetics were studied in rats, analyzing plasma levels of IL4–10 FP upon intravenous injection. In vivo activity was assessed in an inflammatory pain mice model upon intrathecal injection. Results: IL4–10 FP lowSA and IL4–10 FP highSA had similar potency in vitro. The pharmacokinetics study showed a 4-fold higher initial systemic clearance of IL4–10 FP lowSA, whereas the calculated half-life of both IL4–10 FP lowSA and IL4–10 FP highSA was 20.7 min. Finally, both IL4–10 FP glycoforms inhibited persistent inflammatory pain in mice to the same extent. Conclusions: Differential sialylation of IL4–10 fusion protein does not affect the in vitro and in vivo activity, but clearly results in a difference in systemic exposure. The rapid systemic clearance of low sialylated IL4–10 FP could be a favorable characteristic to minimize systemic exposure after administration in a local compartment. [ABSTRACT FROM AUTHOR]

Published
2020
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25. IL4-10 fusion protein is a Novel drug to Treat persistent inflammatory pain

Author

Eijkelkamp, Niels, Steen-Louws, Cristine, Hartgring, Sarita A Y, Willemen, Hanneke L D M, Prado, Judith, Lafeber, Floris P J G, Heijnen, Cobi J., Hack, C. E., van Roon, Joel A G, Kavelaars, Annemieke, Eijkelkamp, Niels, Steen-Louws, Cristine, Hartgring, Sarita A Y, Willemen, Hanneke L D M, Prado, Judith, Lafeber, Floris P J G, Heijnen, Cobi J., Hack, C. E., van Roon, Joel A G, and Kavelaars, Annemieke

Published
2016

26. IL4-10 fusion protein is a Novel drug to Treat persistent inflammatory pain

Author

CTI Eijkelkamp, DDOD, Child Health, Infection & Immunity, Translationele immunologie, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, CTI, Lab exp immunologie / biomarkers ontst., Eijkelkamp, Niels, Steen-Louws, Cristine, Hartgring, Sarita A Y, Willemen, Hanneke L D M, Prado, Judith, Lafeber, Floris P J G, Heijnen, Cobi J., Hack, C. E., van Roon, Joel A G, Kavelaars, Annemieke, CTI Eijkelkamp, DDOD, Child Health, Infection & Immunity, Translationele immunologie, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, CTI, Lab exp immunologie / biomarkers ontst., Eijkelkamp, Niels, Steen-Louws, Cristine, Hartgring, Sarita A Y, Willemen, Hanneke L D M, Prado, Judith, Lafeber, Floris P J G, Heijnen, Cobi J., Hack, C. E., van Roon, Joel A G, and Kavelaars, Annemieke

Published
2016

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