Small Interfering RNA Therapeutic Inclisiran: A New Approach to Targeting PCSK9

German, Charles; Shapiro, Michael D.

doi:10.1007/s40259-019-00399-6

Cited by 78 publications

(65 citation statements)

References 38 publications

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“…The introduction of PCSK9 inhibitors is a milestone in the treatment of FH, and Inclisiran provides a new lipid-lowering technology. The clinical trials of the Inclisiran series of drugs are expected to produce a revolutionary new lipid-lowering drug ( German and Shapiro, 2020 ).…”

Section: From Diagnosis Methods To Therapy Strategies Of Fh Based On mentioning

confidence: 99%

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PCSK9 Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis

2020

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Autosomal dominant familial hypercholesterolemia (FH) affects approximately 1/250, individuals and potentially leads to elevated blood cholesterol and a significantly increased risk of atherosclerosis. Along with improvements in detection and the increased early diagnosis and treatment, the serious burden of FH on families and society has become increasingly apparent. Since FH is strongly associated with proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), increasing numbers of studies have focused on finding effective diagnostic and therapeutic methods based on PCSK9 . At present, as PCSK9 is one of the main pathogenic FH genes, its contribution to FH deserves more explorative research.

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Section: From Diagnosis Methods To Therapy Strategies Of Fh Based On mentioning

confidence: 99%

“… Function and regulation related to PCSK9 and existing/potential therapies for PCSK9 inhibition (adopted and redrawn from Hovingh et al, 2013 ; German and Shapiro, 2020 ). …”

Section: Molecular and Biological Mechanisms To Explore The Influencementioning

confidence: 99%

PCSK9 Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis

2020

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“…The biogenesis of miRNAs is a complex process that requires two endonucleases, Drosha and Dices, and the nuclear transport receptor Exportin 5 (XPO5) ( Figure 4 ) [ 94 ]. The miRNAs, along with other less-known non-coding RNAs, as piwi-interacting RNA (piRNA), small-interfering RNA (siRNA), and small nucleolar RNA (snoRNA), regulate gene expression in some mechanism, including heterochromatin formation and inhibition of translation [ 95 , 96 , 97 ].…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

How Does Protein Nutrition Affect the Epigenetic Changes in Pig? A Review

Marín-Garcia

Llobat

2021

Animals

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Epigenetic changes regulate gene expression and depend of external factors, such as environment and nutrition. In pigs, several studies on protein nutrition have been performed to improve productive and reproductive traits. Indeed, these studies aimed not only to determine broad protein requirements but also pigs’ essential amino acids requirements. Moreover, recent studies tried to determine these nutritional requirements for each individual, which is known as protein precision nutrition. However, nutritional changes could affect different epigenetic mechanisms, modifying metabolic pathways both in a given individual and its offspring. Modifications in protein nutrition, such as change in the amino acid profile, increase or decrease in protein levels, or the addition of metabolites that condition protein requirements, could affect the regulation of some genes, such as myostatin, insulin growth factor, or genes controlling cholesterol and glucose metabolism pathways. This review summarizes the impact of most common protein nutritional strategies on epigenetic changes and describes their effects on regulation of gene expression in pigs. In a context where animal nutrition is shifting towards precision protein nutrition (PPN), further studies evaluating the effects of PPN on animal epigenetic are necessary.

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“…Results from ORION-11 demonstrated that the rate of the adverse events was similar between placebo and treated arm as well as the cardiovascular endpoint such as cardiac death, cardiac arrest, MI and stroke occurred in 7,8% of patients treated with Inclisiran, while it was 10.3% for the placebo group. To further establish the safety, tolerability and efficacy, ORION-4, a phase III double-blinded, will be conducted in 150 sites across the UK and USA to assess the effects of 300 mg SC at day Inclisiran on MACE among the subjects with ASCVD [116].…”

Section: Small Interfering Rna (Inclisiran)mentioning

confidence: 99%

Progress and prospects of biological approaches targeting PCSK9 for cholesterol-lowering, from molecular mechanism to clinical efficacy

Malvandi

Canclini

Alliaj

et al. 2020

Expert Opinion on Biological Therapy

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Introduction: Cardiovascular disorders are one of the leading causes of mortality and morbidity worldwide. Recent advances showed a promising role of proprotein convertase subtilisin/kexin type 9 (PCSK9) as a critical player in regulating plasma LDL levels and lipid metabolism. Areas covered: This review addresses the molecular functions of PCSK9 with a vision on the clinical progress of utilizing monoclonal antibodies and other biological approaches to block PCSK9 activity. The successful clinical trials with monoclonal antibodies are reviewed. Recent advances in (pre)clinical trials of other biological approaches, such as small interfering RNAs, are also discussed. Expert opinion: Discovery of PCSK9 and clinical use of its inhibitors to manage lipid metabolism is a step forward in hypolipidaemic therapy. A better understanding of the molecular activity of PCSK9 can help to identify new approaches in the inhibition of PCSK9 expression/activity. Whether if PCSK9 plays a role in other cardiometabolic conditions may provide grounds for further development of therapies.

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Small Interfering RNA Therapeutic Inclisiran: A New Approach to Targeting PCSK9

Cited by 78 publications

References 38 publications

PCSK9 Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis

PCSK9 Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis

How Does Protein Nutrition Affect the Epigenetic Changes in Pig? A Review

Progress and prospects of biological approaches targeting PCSK9 for cholesterol-lowering, from molecular mechanism to clinical efficacy

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