Clinical Pharmacokinetics and Pharmacodynamics of CSL112

Ortega‐Paz, Luis; Giordano, Salvatore; Capodanno, Davide; Mehran, Roxana; Gibson, C. Michael; Angiolillo, Dominick J.

doi:10.1007/s40262-023-01224-8

Cited by 7 publications

(3 citation statements)

References 48 publications

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“…There is currently a phase 3 trial underway assessing the potential of recombinant ApoA1 in reconstituted HDL (CSL112) as a therapeutic strategy for preventing early recurrent cardiovascular events after a myocardial infarction ( 51 ). CSL112 has demonstrated a dose-dependent increase in cholesterol efflux, reaching up to a 4-fold increase in healthy adult subjects ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of missense variants affecting the extracellular domains of ABCA1 using a fluorescence-based assay

Teigen,

Ølnes,

Bjune

et al. 2024

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Functional characterization of missense variants affecting the extracellular domains of ABCA1 using a fluorescence-based assay

Teigen,

Ølnes,

Bjune

et al. 2024

Journal of Lipid Research

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“…In vitro treatments with CSL111 suppressed TLR2 expression and downstream nuclear factor kappa B (NF-κB) activation through the myeloid differentiation primary response 88 (MYD88) signaling arm in human macrophages [ 204 ]. CSL112 infusion decreased markers of plaque instability such as matrix metalloproteinase 9 and MCP-1 and pro-inflammatory cytokines such as interleukin-1β (IL-1β) [ 222 ].…”

Section: Anti-inflammatory Effects Of Synthetic/reconstituted Hdl Mim...mentioning

confidence: 99%

A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease

Rani

Marsche

2023

Pharmaceutics

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High-density lipoproteins (HDL) are complex endogenous nanoparticles involved in important functions such as reverse cholesterol transport and immunomodulatory activities, ensuring metabolic homeostasis and vascular health. The ability of HDL to interact with a plethora of immune cells and structural cells places it in the center of numerous disease pathophysiologies. However, inflammatory dysregulation can lead to pathogenic remodeling and post-translational modification of HDL, rendering HDL dysfunctional or even pro-inflammatory. Monocytes and macrophages play a critical role in mediating vascular inflammation, such as in coronary artery disease (CAD). The fact that HDL nanoparticles have potent anti-inflammatory effects on mononuclear phagocytes has opened new avenues for the development of nanotherapeutics to restore vascular integrity. HDL infusion therapies are being developed to improve the physiological functions of HDL and to quantitatively restore or increase the native HDL pool. The components and design of HDL-based nanoparticles have evolved significantly since their initial introduction with highly anticipated results in an ongoing phase III clinical trial in subjects with acute coronary syndrome. The understanding of mechanisms involved in HDL-based synthetic nanotherapeutics is critical to their design, therapeutic potential and effectiveness. In this review, we provide a current update on HDL-ApoA-I mimetic nanotherapeutics, highlighting the scope of treating vascular diseases by targeting monocytes and macrophages.

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“…In patients with T2D, CSL-111 increases the ex vivo capability of HDLs to inhibit the expression of adhesion molecules on endothelial cells and decrease the expression of CD11b on leukocytes [181]. CSL-112, composed of two molecules of apoA-I and 110 molecules of phosphatidylcholine, appears as one of the most promising HDL mimetics [191,192]. CSL-112 particles were rapidly remodelled after infusion in humans, resulting in particular in the formation of small highly functional HDL particles [187].…”

Section: Effects Of Treatment With Hdl Mimetics On Oxidative Stress A...mentioning

confidence: 99%

Antioxidant and Anti-Inflammatory Functions of High-Density Lipoprotein in Type 1 and Type 2 Diabetes

Denimal

2023

Antioxidants

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(1) Background: high-density lipoproteins (HDLs) exhibit antioxidant and anti-inflammatory properties that play an important role in preventing the development of atherosclerotic lesions and possibly also diabetes. In turn, both type 1 diabetes (T1D) and type 2 diabetes (T2D) are susceptible to having deleterious effects on these HDL functions. The objectives of the present review are to expound upon the antioxidant and anti-inflammatory functions of HDLs in both diabetes in the setting of atherosclerotic cardiovascular diseases and discuss the contributions of these HDL functions to the onset of diabetes. (2) Methods: this narrative review is based on the literature available from the PubMed database. (3) Results: several antioxidant functions of HDLs, such as paraoxonase-1 activity, are compromised in T2D, thereby facilitating the pro-atherogenic effects of oxidized low-density lipoproteins. In addition, HDLs exhibit diminished ability to inhibit pro-inflammatory pathways in the vessels of individuals with T2D. Although the literature is less extensive, recent evidence suggests defective antiatherogenic properties of HDL particles in T1D. Lastly, substantial evidence indicates that HDLs play a role in the onset of diabetes by modulating glucose metabolism. (4) Conclusions and perspectives: impaired HDL antioxidant and anti-inflammatory functions present intriguing targets for mitigating cardiovascular risk in individuals with diabetes. Further investigations are needed to clarify the influence of glycaemic control and nephropathy on HDL functionality in patients with T1D. Furthermore, exploring the effects on HDL functionality of novel antidiabetic drugs used in the management of T2D may provide intriguing insights for future research.

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Clinical Pharmacokinetics and Pharmacodynamics of CSL112

Cited by 7 publications

References 48 publications

Functional characterization of missense variants affecting the extracellular domains of ABCA1 using a fluorescence-based assay

Functional characterization of missense variants affecting the extracellular domains of ABCA1 using a fluorescence-based assay

A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease

Antioxidant and Anti-Inflammatory Functions of High-Density Lipoprotein in Type 1 and Type 2 Diabetes

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