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Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
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Pharmacogenomics: Identification of New Drug Targets01:29

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Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
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Emerging biologic therapies for hypercholesterolaemia.

Giacomo Pucci1,2, Arrigo F Cicero3, Claudio Borghi3

  • 1a Dipartimento di Medicina , Università di Perugia , Perugia , Italy.

Expert Opinion on Biological Therapy
|June 16, 2017
PubMed
Summary

Monoclonal antibodies targeting PCSK9 effectively lower LDL-cholesterol, reducing cardiovascular disease risk. Further LDL-C reduction with PCSK9 inhibition offers enhanced protection for high-risk individuals.

Keywords:
HypercholesterolemiaLDL cholesterolPCSK9alirocumabbiologic therapycardiovascular diseasecardiovascular riskdyslipidemiaevolocumablipoproteinsproprotein convertase subtilisin/kexin type 9 inhibitors

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Area of Science:

  • Cardiology
  • Pharmacology
  • Biochemistry

Background:

  • Low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for cardiovascular disease (CV).
  • Therapies reducing LDL-C are proven effective in mitigating atherosclerotic CV disease risk.
  • Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) represent a novel therapeutic approach.

Purpose of the Study:

  • To review the efficacy of PCSK9-targeting mAbs in reducing LDL-C and other atherogenic lipids.
  • To discuss the implications of bococizumab's discontinuation and inclisiran's development.
  • To evaluate the role of PCSK9 inhibition in enhancing cardiovascular protection.

Main Methods:

  • Review of current literature on PCSK9 inhibitors.
  • Analysis of clinical trial data for PCSK9 monoclonal antibodies and inclisiran.
  • Discussion of cardiovascular outcomes and safety profiles.

Main Results:

  • PCSK9 inhibition effectively lowers LDL-C and other atherogenic lipid fractions.
  • Bococizumab development was halted due to safety and efficacy issues.
  • Inclisiran shows promise as a long-acting PCSK9 inhibitor.
  • Early data suggest additional CV protection with PCSK9 inhibition alongside standard therapies in high-risk patients.

Conclusions:

  • PCSK9 inhibition, particularly with mAbs, offers a significant advancement in LDL-C reduction strategies.
  • Further LDL-C lowering via PCSK9 inhibition may provide additional cardiovascular protection for high-risk populations.
  • These therapies have the potential to reshape cardiovascular risk management, though cost-effectiveness requires further evaluation.