Lipid-lowering therapy: Guidelines to precision medicine

X, Su; Cheng, Yufeng; Chang, Dong

doi:10.1016/j.cca.2020.12.019

Cited by 13 publications

(12 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, the proper use of statins in patients with NAFLD to prevent the development and complications of atherosclerosis in patients at a high risk is very relevant considering that these drugs are often underprescribed [ 156 ]. Of note, in the near future a precision medicine approach to lipid-lowering therapy is also envisioned [ 158 ].…”

Section: Tailoring Nafld Management To Individual Patientsmentioning

confidence: 99%

Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management

Lonardo¹,

Arab

Arrese

2021

Adv Ther

View full text Add to dashboard Cite

Precision medicine defines the attempt to identify the most effective approaches for specific subsets of patients based on their genetic background, clinical features, and environmental factors. Nonalcoholic fatty liver disease (NAFLD) encompasses the alcohol-like spectrum of liver disorders (steatosis, steatohepatitis with/without fibrosis, and cirrhosis and hepatocellular carcinoma) in the nonalcoholic patient. Recently, disease renaming to MAFLD [metabolic (dysfunction)-associated fatty liver disease] and positive criteria for diagnosis have been proposed. This review article is specifically devoted to envisaging some clues that may be useful to implementing a precision medicine-oriented approach in research and clinical practice. To this end, we focus on how sex and reproductive status, genetics, intestinal microbiota diversity, endocrine and metabolic status, as well as physical activity may interact in determining NAFLD/ MAFLD heterogeneity. All these factors should be considered in the individual patient with the aim of implementing an individualized therapeutic plan. The impact of considering NAFLD heterogeneity on the development of targeted therapies for NAFLD subgroups is also extensively discussed.

show abstract

Section: Tailoring Nafld Management To Individual Patientsmentioning

confidence: 99%

Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management

Lonardo¹,

Arab

Arrese

2021

Adv Ther

View full text Add to dashboard Cite

show abstract

“…Unfortunately, the PPAR-α/γ agonist had been reported to increase about 2–4% of body weight and had adverse reactions including peripheral oedema in probably 5% of treated patients and fatal heart failure in approximately 11% of treated patients [ 40 ]. The classical lipids-reducing agents statins were not applicable to NAFLD as for its intolerance or side effects [ 41 ]. Thus, safe and efficient targets for NAFLD are urgently needed.…”

Section: Discussionmentioning

confidence: 99%

A novel nanobody-heavy chain antibody against Angiopoietin-like protein 3 reduces plasma lipids and relieves nonalcoholic fatty liver disease

Fan

et al. 2022

J Nanobiotechnol

View full text Add to dashboard Cite

Background Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease mainly on account of hypercholesterolemia and may progress to cirrhosis and hepatocellular carcinoma. The discovery of effective therapy for NAFLD is an essential unmet need. Angiopoietin-like protein 3 (ANGPTL3), a critical lipid metabolism regulator, resulted in increased blood lipids and was elevated in NAFLD. Here, we developed a nanobody-heavy chain antibody (VHH-Fc) to inhibit ANGPTL3 for NAFLD treatment. Results In this study, we retrieved an anti-ANGPTL3 VHH and Fc fusion protein, C44-Fc, which exhibited high affinities to ANGPTL3 proteins and rescued ANGPLT3-mediated inhibition of lipoprotein lipase (LPL) activity. The C44-Fc bound a distinctive epitope within ANGPTL3 when compared with the approved evinacumab, and showed higher expression yield. Meanwhile, C44-Fc had significant reduction of the triglyceride (~ 44.2%), total cholesterol (~ 36.6%) and LDL-cholesterol (~ 54.4%) in hypercholesterolemic mice and ameliorated hepatic lipid accumulation and liver injury in NAFLD mice model. Conclusions We discovered a VHH-Fc fusion protein with high affinity to ANGPTL3, strong stability and also alleviated the progression of NAFLD, which might offer a promising therapy for NAFLD. Graphical Abstract

show abstract

“…NAFLD is a metabolic disease and positively associated with hypercholesterolemia that is increasingly acknowledged as the key factor of excessive lipid uptake and lipotoxicity in liver resulting in pathologic insult. 3,41 It is projected to develop into cirrhosis with increasing risk of hepatocellular carcinoma and may be the main inducement of liver transplantation. 42 Despite its prevalence and seriousness, NAFLD still lacks effective therapeutics.…”

Section: Discussionmentioning

confidence: 99%

“…40 The traditional lipidsreducing agents statins were not applicable to NAFLD treatment as for its intolerance or side effects. 41 Thus, a safe and e cient targets for NAFLD is urgently needed. ANGPTL3, as a depressor of LPL and EL, was recently revealed elevated expression levels in liver of NAFLD patients and contributed to increased circulating ANGPTL3.…”

Section: Discussionmentioning

confidence: 99%

A Novel Nanobody-Heavy Chain Antibody Against Angiopoietin-Like Protein 3 Reduces Plasma Lipids and Relieves Nonalcoholic Fatty Liver Disease

Fan

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease mainly on account of hypercholesterolemia and may progresses to cirrhosis and hepatocellular carcinoma. The discovery of effective therapies for NAFLD is a critical unmet need. Angiopoietin-like protein 3 (ANGPTL3), a critical lipid metabolism regulator, cause elevated blood lipids and are elevated in NAFLD. Here, we develop a nanobody-heavy chain antibody (VHH-Fc) to inhibit ANGPTL3 for NAFLD treatment. Results In this study, we screened out a anti-ANGPTL3 VHH and Fc fusion protein, C44-Fc, which exhibited a high affinity to human and mouse ANGPTL3 proteins at 0.1402~0.2088 nM and rescued ANGPLT3-mediated inhibition of lipoprotein lipase (LPL) activity. The C44-Fc had different ANGPTL3 binding epitope, a double expression yield and better thermostability when compared with the evinacumab, maintaining no obvious degradation or aggregation at low and high pH, 40°C for 28 days, and freeze-thaw. Furthermore, C44-Fc significantly ameliorated the triglyceride (~44.2%), total cholesterol (~36.6%) and LDL-cholesterol (~54.4%) levels in hypercholesterolemic mice and ameliorated hepatic lipid accumulation and liver injury in NAFLD mice. Conclusions We discover a VHH-Fc fusion protein with high affinity to ANGPTL3 and alleviates the progression of NAFLD, which offers a prospective therapy for NAFLD.

show abstract

Lipid-lowering therapy: Guidelines to precision medicine

Cited by 13 publications

References 84 publications

Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management

Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management

A novel nanobody-heavy chain antibody against Angiopoietin-like protein 3 reduces plasma lipids and relieves nonalcoholic fatty liver disease

A Novel Nanobody-Heavy Chain Antibody Against Angiopoietin-Like Protein 3 Reduces Plasma Lipids and Relieves Nonalcoholic Fatty Liver Disease

Contact Info

Product

Resources

About