A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of AEM-28 in Healthy Subjects and Patients With Refractory Hypercholesterolemia

The purpose of the first part of this study is to determine the safety and tolerability of a single dose of AEM-28, an apolipoprotein E mimetic, in subjects with high total cholesterol who are otherwise healthy subjects. The pharmacokinetics and pharmacodynamics of AEM-28 will also be evaluated.
The second part of this study will be a multiple ascending dose evaluation of AEM-28 in patients with refractory hypercholesterolemia.
AEM-28 has demonstrated significant lipid lowering activity and positive effects on the artery wall. AEM-28 is being developed for the treatment of homozygous familial hypercholesterolemia.

Start Date01 Mar 2014

Sponsor / Collaborator

LipimetiX Development LLC

100 Clinical Results associated with AEM-28

100 Translational Medicine associated with AEM-28

100 Patents (Medical) associated with AEM-28

Literatures (Medical) associated with AEM-28

01 Jan 2024·Journal of Colloid and Interface Science

Characterization of nanodisc-forming peptides for membrane protein studies

Article

Author: Auchus, Richard ; Ramamoorthy, Ayyalusamy ; Im, Sang-Choul ; Krishnarjuna, Bankala ; Sharma, Gaurav ; Anantharamaiah, G M

Lipid-bilayer nanodiscs provide a stable, native-like membrane environment for the functional and structural studies of membrane proteins and other membrane-binding molecules. Peptide-based nanodiscs having unique properties are developed for membrane protein studies and other biological applications. While the self-assembly process rendering the formation of peptide-nanodiscs is attractive, it is important to understand the stability and suitability of these nanodisc systems for membrane protein studies. In this study, we investigated the nanodiscs formation by the anti-inflammatory and tumor-suppressing peptide AEM28. AEM28 is a chimeric peptide containing a cationic-rich heparan sulfate proteoglycan- (HSPG)-binding domain from human apolipoprotein E (hapoE) (141-150) followed by the 18A peptide's amino acid sequence. AEM28-based nanodiscs made with different types of lipids were characterized using various biophysical techniques and compared with the nanodiscs formed using 2F or 4F peptides. Variable temperature dynamic light-scattering and ³¹P NMR experiments indicated the fusion and size heterogeneity of nanodiscs at high temperatures. The suitability of AEM28 and Ac-18A-NH_2- (2F-) based nanodiscs for studying membrane proteins is demonstrated by reconstituting and characterizing a drug-metabolizing enzyme, cytochrome-P450 (CYP450), or the redox complex CYP450-CYP450 reductase. AEM28 and 2F were also tested for their efficacies in solubilizing E. coli membranes to understand the possibility of using them for detergent-free membrane protein isolation. Our experimental results suggest that AEM28 nanodiscs are suitable for studying membrane proteins with a net positive charge, whereas 2F-based nanodiscs are compatible with any membrane proteins and their complexes irrespective of their charge. Furthermore, both peptides solubilized E. coli cell membranes, indicating their use in membrane protein isolation and other applications related to membrane solubilization.

05 Jan 2020·Journal of Cancer Research and Therapeutic Oncology

Bovine HDL and Dual Domain HDL-Mimetic Peptides Inhibit Tumor Develop- ment in Mice

Article

Author: Wu, Yanyuan ; White, C Roger ; Pietras, Richard ; Gm, Anantharamaiah ; Palgunachari, Mayakonda N ; Farias-Eisner, Robin ; Stessman, Holly ; Reddy, Srinivasa T ; Vadgama, Jay ; Nguyen, Dorothy ; Su, Feng

A growing body of literature supports the role of apolipoproteins present in HDL in the treatment of pro-inflammatory diseases including cancer. We examined whether bovine HDL (bHDL) and three dual-domain peptides, namely AEM-28 and its analog AEM-28-2, and HM-10/10, affect tumor growth and development in mouse models of ovarian and colon cancer. We demonstrate that bHDL inhibits mouse colorectal cancer cell line CT26-mediated lung tumor development, and mouse ovarian cancer cell line ID8-mediated tumor burden. We also demonstrate that, although to different degrees, dual-domain peptides inhibit cell viability of mouse and human ovarian and colon cancer cell lines, but not that of normal human colonic epithelial cells or NIH3T3 mouse fibroblasts. Dual-domain peptides administered subcutaneously or in a chow diet decrease CT26 cell-mediated tumor burden, tumor growth, and tumor dissemination in BALB/c mice. Plasma levels of lysophosphatidic acid (LPA) are significantly reduced in mice that received bHDL and the dual-domain peptides, suggesting that reduction by effecting accumulation and/or synthesis of pro-inflammatory lipids may be one of the mechanisms for the inhibition of tumor development by bHDL and the dual-domain peptides. Our studies suggest that therapeutics based on apolipoproteins present in HDL may be novel agents for the treatment of epithelial adenocarcinomas of the ovary and colon.

01 Oct 2014·Journal of Lipid ResearchQ2 · BIOLOGY

Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review

Q2 · BIOLOGY

Review

Author: White, C Roger ; Anantharamaiah, G M ; Garber, David W

Reduced levels of HDL cholesterol (HDL-C) are a strong independent predictor of coronary artery disease (CAD) risk. The major anti-atherogenic function of HDL is to mediate reverse cholesterol transport. This response is highly dependent on apoA-I and apoE, protein components of HDL. Randomized clinical trials have assessed effects of several classes of drugs on plasma cholesterol levels in CAD patients. Agents including cholestyramine, fibrates, niacin, and statins significantly lower LDL cholesterol (LDL-C) and induce modest increases in HDL-C, but tolerance issues and undesirable side effects are common. Additionally, residual risk may be present in patients with persistently low HDL-C and other complications despite a reduction in LDL-C. These observations have fueled interest in the development of new pharmacotherapies that positively impact circulating lipoproteins. The goal of this review is to discuss the therapeutic potential of synthetic apolipoprotein mimetic peptides. These include apoA-I mimetic peptides that have undergone initial clinical assessment. We also discuss newer apoE mimetics that mediate the clearance of atherogenic lipids from the circulation and possess anti-inflammatory properties. One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials.

100 Deals associated with AEM-28

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperlipidemia Type IIa	Phase 3	AU	LipimetiX Development LLC	26 May 2014
Hypercholesterolemia	Phase 2	-	Anji Pharmaceuticals, Inc.Startup	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02100839 (CTgov)	Phase 1/2	Hypercholesterolemia \| Hyperlipoproteinemia Type II	52	AEM-28 (AEM-28)	gqqsgxfivs(jeakfcqczx) = spnppyhfuw vzhjccncte (faxqqbdcvh, bosbyltlue - aebbgngvum) View more	-	29 Dec 2015
				Normal Saline (Normal Saline)	gqqsgxfivs(jeakfcqczx) = iaxuvscszn vzhjccncte (faxqqbdcvh, ujmgmyxzpk - ngshhsxiab) View more

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