New drugs for cholesterol
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New Drugs for Cholesterol Management
Introduction to Cholesterol-Lowering Drugs
Cholesterol management is crucial for reducing the risk of cardiovascular diseases. While statins have been the cornerstone of cholesterol-lowering therapy, new drugs are emerging to address the limitations of existing treatments and provide additional options for patients who are statin-intolerant or require further LDL-C reduction.
Oligonucleotide Therapeutics: siRNA
A promising new class of cholesterol-lowering drugs involves small interfering RNA (siRNA) therapeutics. These chemically modified siRNAs, conjugated to trivalent N-acetylgalactosamine, work by destroying RNA before protein synthesis, effectively reducing cholesterol levels . Inclisiran, a notable siRNA, has shown significant efficacy in lowering LDL cholesterol.
PCSK9 Inhibitors
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are another innovative class of drugs. These monoclonal antibodies target and inhibit PCSK9, a protein that degrades LDL receptors, thereby increasing the clearance of LDL cholesterol from the bloodstream. Clinical trials have demonstrated that PCSK9 inhibitors can reduce LDL cholesterol levels by up to 61% when used in combination with statins. This class includes drugs like REGN727 and AMG 145, which have shown promising results in reducing cholesterol levels significantly.
Berberine: A Novel Mechanism
Berberine (BBR), a compound derived from a Chinese herb, has emerged as a novel cholesterol-lowering agent. Unlike statins, BBR works by upregulating LDL receptor expression through a post-transcriptional mechanism that stabilizes LDLR mRNA. Clinical studies have shown that BBR can reduce serum cholesterol by 29% and LDL cholesterol by 25% in hypercholesterolemic patients.
ATP Citrate Lyase Inhibitors
Bempedoic acid, an ATP citrate lyase inhibitor, is another new drug that targets cholesterol synthesis upstream of the HMG-CoA reductase pathway. This drug has shown efficacy in lowering LDL cholesterol, particularly in patients who are statin-intolerant or require additional LDL-C reduction .
Cholesterol Absorption Inhibitors
Ezetimibe, a cholesterol absorption inhibitor, works by preventing the absorption of cholesterol in the intestines. When used alone or in combination with statins, ezetimibe has been effective in further lowering LDL cholesterol levels. Other agents like avasimibe and implitapide are also being investigated for their potential to inhibit intestinal cholesterol absorption.
Antisense Oligonucleotides
Antisense oligonucleotides (ASOs) are designed to bind to specific mRNA sequences, preventing the production of target proteins. Mipomersen, an ASO targeting apolipoprotein B-100, has been approved for the treatment of homozygous familial hypercholesterolemia and has shown significant LDL-C reduction.
Conclusion
The landscape of cholesterol-lowering therapies is rapidly evolving with the introduction of new drugs targeting various mechanisms of cholesterol metabolism. These emerging therapies, including siRNA, PCSK9 inhibitors, berberine, ATP citrate lyase inhibitors, cholesterol absorption inhibitors, and antisense oligonucleotides, offer promising alternatives and adjuncts to traditional statin therapy. As research continues, these new drugs hold the potential to significantly improve cholesterol management and reduce cardiovascular risk in diverse patient populations.
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