Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc)
Inflammation is a strong driver of atherosclerotic cardiovascular disease (ASCVD). There is a large unmet need for therapies that prevent or reduce excessive inflammation while avoiding systemic immunosuppression. We showed previously that selective inhibition of pro-inflammatory interleukin-6 (IL-6...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.758233/full |
| _version_ | 1818238657900838912 |
|---|---|
| author | Dominik M. Schulte Dominik M. Schulte Georg H. Waetzig Georg H. Waetzig Harald Schuett Marlies Marx Berenice Schulte Christoph Garbers Juliane Lokau Ann-Kathrin Vlacil Juliane Schulz Anna K. Seoudy Bernhard Schieffer Philip Rosenstiel Marcus Seeger Matthias Laudes Matthias Laudes Stefan Rose-John Ulf Lützen Karsten Grote Stefan Schreiber Stefan Schreiber |
| author_facet | Dominik M. Schulte Dominik M. Schulte Georg H. Waetzig Georg H. Waetzig Harald Schuett Marlies Marx Berenice Schulte Christoph Garbers Juliane Lokau Ann-Kathrin Vlacil Juliane Schulz Anna K. Seoudy Bernhard Schieffer Philip Rosenstiel Marcus Seeger Matthias Laudes Matthias Laudes Stefan Rose-John Ulf Lützen Karsten Grote Stefan Schreiber Stefan Schreiber |
| author_sort | Dominik M. Schulte |
| collection | DOAJ |
| description | Inflammation is a strong driver of atherosclerotic cardiovascular disease (ASCVD). There is a large unmet need for therapies that prevent or reduce excessive inflammation while avoiding systemic immunosuppression. We showed previously that selective inhibition of pro-inflammatory interleukin-6 (IL-6) trans-signalling by the fusion protein olamkicept (sgp130Fc) prevented and reduced experimental murine atherosclerosis in low-density lipoprotein receptor-deficient (Ldlr−/−) mice on a high-fat, high-cholesterol diet independently of low-density lipoprotein (LDL) cholesterol metabolism. Therefore, we allowed compassionate use of olamkicept (600 mg intravenously biweekly for 10 weeks) in a patient with very-high-risk ASCVD. Despite optimal LDL cholesterol under maximum tolerated lipid-lowering treatment, the patient had a remaining very high risk for future cardiovascular events related to significant arterial wall inflammation with lipoprotein (a) [Lp(a)]-cholesterol as the main contributor. 18Fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT) measurements were performed before and after the treatment period. Olamkicept reduced arterial wall inflammation in this patient without interfering with lipoprotein metabolism. No clinical or laboratory side effects were observed during or after treatment with olamkicept. Our findings in this patient matched the results from our mechanistic study in Ldlr−/− mice, which were extended by additional analyses on vascular inflammation. Olamkicept may be a promising option for treating ASCVD independently of LDL cholesterol metabolism. A Phase II trial of olamkicept in ASCVD is currently being prepared. |
| first_indexed | 2024-12-12T12:45:09Z |
| format | Article |
| id | doaj.art-d984510475674274bd6408ba7e87d06a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T12:45:09Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d984510475674274bd6408ba7e87d06a2022-12-22T00:24:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.758233758233Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc)Dominik M. Schulte0Dominik M. Schulte1Georg H. Waetzig2Georg H. Waetzig3Harald Schuett4Marlies Marx5Berenice Schulte6Christoph Garbers7Juliane Lokau8Ann-Kathrin Vlacil9Juliane Schulz10Anna K. Seoudy11Bernhard Schieffer12Philip Rosenstiel13Marcus Seeger14Matthias Laudes15Matthias Laudes16Stefan Rose-John17Ulf Lützen18Karsten Grote19Stefan Schreiber20Stefan Schreiber21Department of Internal Medicine I, University Medical Center Schleswig-Holstein (UKSH), Kiel, GermanyInstitute of Diabetes and Clinical Metabolic Research, Kiel University and UKSH, Kiel, GermanyInstitute of Clinical Molecular Biology, Kiel University and UKSH, Kiel, GermanyCONARIS Research Institute AG, Kiel, GermanyDepartment of Cardiology and Angiology, Philipps-University, Marburg, GermanyDepartment of Nuclear Medicine, Molecular Imaging Diagnostics and Therapy, UKSH, Kiel, GermanyDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein (UKSH), Kiel, GermanyDepartment of Pathology, Otto-von-Guericke-University, Magdeburg, GermanyDepartment of Pathology, Otto-von-Guericke-University, Magdeburg, GermanyDepartment of Cardiology and Angiology, Philipps-University, Marburg, GermanyDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein (UKSH), Kiel, GermanyDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein (UKSH), Kiel, GermanyDepartment of Cardiology and Angiology, Philipps-University, Marburg, GermanyInstitute of Clinical Molecular Biology, Kiel University and UKSH, Kiel, GermanyDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein (UKSH), Kiel, GermanyDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein (UKSH), Kiel, GermanyInstitute of Diabetes and Clinical Metabolic Research, Kiel University and UKSH, Kiel, GermanyBiochemical Institute, Kiel University, Kiel, GermanyDepartment of Nuclear Medicine, Molecular Imaging Diagnostics and Therapy, UKSH, Kiel, GermanyDepartment of Cardiology and Angiology, Philipps-University, Marburg, GermanyDepartment of Internal Medicine I, University Medical Center Schleswig-Holstein (UKSH), Kiel, GermanyInstitute of Clinical Molecular Biology, Kiel University and UKSH, Kiel, GermanyInflammation is a strong driver of atherosclerotic cardiovascular disease (ASCVD). There is a large unmet need for therapies that prevent or reduce excessive inflammation while avoiding systemic immunosuppression. We showed previously that selective inhibition of pro-inflammatory interleukin-6 (IL-6) trans-signalling by the fusion protein olamkicept (sgp130Fc) prevented and reduced experimental murine atherosclerosis in low-density lipoprotein receptor-deficient (Ldlr−/−) mice on a high-fat, high-cholesterol diet independently of low-density lipoprotein (LDL) cholesterol metabolism. Therefore, we allowed compassionate use of olamkicept (600 mg intravenously biweekly for 10 weeks) in a patient with very-high-risk ASCVD. Despite optimal LDL cholesterol under maximum tolerated lipid-lowering treatment, the patient had a remaining very high risk for future cardiovascular events related to significant arterial wall inflammation with lipoprotein (a) [Lp(a)]-cholesterol as the main contributor. 18Fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT) measurements were performed before and after the treatment period. Olamkicept reduced arterial wall inflammation in this patient without interfering with lipoprotein metabolism. No clinical or laboratory side effects were observed during or after treatment with olamkicept. Our findings in this patient matched the results from our mechanistic study in Ldlr−/− mice, which were extended by additional analyses on vascular inflammation. Olamkicept may be a promising option for treating ASCVD independently of LDL cholesterol metabolism. A Phase II trial of olamkicept in ASCVD is currently being prepared.https://www.frontiersin.org/articles/10.3389/fphar.2022.758233/fullatherosclerosiscase reportinterleukin-6olamkiceptsgp130Fc |
| spellingShingle | Dominik M. Schulte Dominik M. Schulte Georg H. Waetzig Georg H. Waetzig Harald Schuett Marlies Marx Berenice Schulte Christoph Garbers Juliane Lokau Ann-Kathrin Vlacil Juliane Schulz Anna K. Seoudy Bernhard Schieffer Philip Rosenstiel Marcus Seeger Matthias Laudes Matthias Laudes Stefan Rose-John Ulf Lützen Karsten Grote Stefan Schreiber Stefan Schreiber Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc) Frontiers in Pharmacology atherosclerosis case report interleukin-6 olamkicept sgp130Fc |
| title | Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc) |
| title_full | Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc) |
| title_fullStr | Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc) |
| title_full_unstemmed | Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc) |
| title_short | Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc) |
| title_sort | case report arterial wall inflammation in atherosclerotic cardiovascular disease is reduced by olamkicept sgp130fc |
| topic | atherosclerosis case report interleukin-6 olamkicept sgp130Fc |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.758233/full |
| work_keys_str_mv | AT dominikmschulte casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT dominikmschulte casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT georghwaetzig casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT georghwaetzig casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT haraldschuett casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT marliesmarx casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT bereniceschulte casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT christophgarbers casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT julianelokau casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT annkathrinvlacil casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT julianeschulz casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT annakseoudy casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT bernhardschieffer casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT philiprosenstiel casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT marcusseeger casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT matthiaslaudes casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT matthiaslaudes casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT stefanrosejohn casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT ulflutzen casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT karstengrote casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT stefanschreiber casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc AT stefanschreiber casereportarterialwallinflammationinatheroscleroticcardiovasculardiseaseisreducedbyolamkiceptsgp130fc |