The Application of RNAi Therapeutics for Cardiovascular Disease Treatment

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As of January 2024, approximately 131 RNA-based therapies are being studied in clinical trials. The RNA-based therapy pipeline is growing quickly and spans multiple therapeutic areas, highlighting its potential application across many disease areas.</p> <p>RNA interference (RNAi) silences specific genes that cause disease or contribute to disease <a href="https://www.thermofisher.com/blog/ask-a-scientist/what-is-rnai/" rel="noopener" target="_blank">by binding to messenger RNA (mRNA) to disrupt the production of proteins</a>. Unlike conventional therapies that target proteins, RNAi acts earlier in the process, destroying mRNA before proteins form.</p> <p>The growing understanding of RNA functions and their crucial roles in diseases promoted the <a href="https://www.nature.com/articles/s41419-022-05075-2" rel="noopener" target="_blank">application of various RNAs to selectively function on hitherto "undruggable" proteins, transcripts, and genes</a>, thus potentially broadening the therapeutic targets. Several RNA-based medications have been approved for clinical use, while others are still under investigation.</p> <p><strong>Why do we Need New Approaches to Combat Cardiovascular Disease?</strong></p> <p>Despite available treatments, <a href="https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1" rel="noopener" target="_blank">cardiovascular disease (CVD) is the leading cause of death globally</a>. There are several daily medications on the market to manage symptoms such as high blood pressure, but the patient's medication adherence may be affected; if symptoms are not present the patient may forget to take their medication. Therefore, scientists are seeking innovative approaches to address the risk factors for heart attack, stroke, and other cardiovascular symptoms.</p> <p><a href="https://www.the-scientist.com/the-promise-of-rnai-therapeutics-for-cardiovascular-disease-treatment-72267" rel="noopener" target="_blank">RNAi therapeutics can minimize the levels of unwanted proteins for extended periods which means they can be administered infrequently</a> – every three or six months. This reduces the need for daily medication, lessening the treatment burden for patients.</p> <p><strong>Case Study: Alnylam Pharmaceuticals and RNAi in CVD</strong></p> <p>Alnylam Pharmaceuticals is a biopharmaceutical company exploring the potential of RNAi to treat CVD, a high unmet medical need. The company recently conducted an RNAi therapeutic trial for patients with ATTR-CM, a progressive and fatal disease caused by misfolded transthyretin (TTR) proteins, which build up as amyloid deposits in various parts of the body, including the nerves and heart.</p> <p><strong>Related:</strong></p> <ul> <li><a href="https://oxfordglobal.com/discovery-development/resources/rna-interference-looking-back-at-the-2006-nobel-prize" rel="noopener" target="_blank">RNA Interference: Looking Back at the 2006 Nobel Prize</a></li> <li><a href="https://oxfordglobal.com/discovery-development/resources/small-molecule-targets-toxic-rna-linked-to-als-and-dementia" rel="noopener" target="_blank">Small Molecule Targets Toxic RNA Linked to ALS and Dementia</a>  </li> </ul> <p>HELIOS–B is a phase III study designed to evaluate the efficacy and safety of <a href="https://www.amvuttra.com/">vutrisiran</a>, an RNAi therapeutic that targets the root cause by lowering mutant and normal TTR levels. The trial consisted of 665 adult patients with ATTR-CM on available standard-of-care treatments alongside monotherapy patients who only received vutrisiran.</p> <p>The <a href="https://www.the-scientist.com/the-promise-of-rnai-therapeutics-for-cardiovascular-disease-treatment-72267" rel="noopener" target="_blank">study met primary and secondary endpoints across both sample groups with statistical significance</a>. Moreover, the trial results across both overall and monotherapy populations displayed the reduction of all-cause mortality and recurrent cardiovascular symptoms in patients with ATTR-CM.</p> <p>This is a significant step that brings a CVD therapeutic one step closer to market. Kevin Fitzgerald, CSO at Alnylam Pharmaceuticals said he hopes to expand RNAi's therapeutic potential and explore other treatment avenues in the neuroscience field.</p> <p><strong>Conclusion</strong></p> <p>RNAi therapeutics offer a novel way of treating diseases like CVD by targeting harmful proteins at their genetic source. This represents a key advantage over traditional therapies that act after these proteins are produced.</p> <p>Alnylam Pharmaceuticals’ promising results, from their HELIOS–B study for ATTR-CM, shows RNAi’s potential to reduce mortality and improve patient outcomes. Overall RNAi therapies are well-positioned to transform how scientists investigate complex diseases due to their potential to address previously "undruggable" targets and reduce the treatment burden through infrequent dosing.</p> <div class="content-body-footer"> </div> </div> <div class="content-sidebar"> <div class="related-articles"> <h3 class="center">Related Resources</h3> <div class="article"> <a href="/discovery-development/resources/sponsored/case-studies/ardigen/advancing-drug-discovery-through-innovative-technologies-strategic-collaboration"> <div class="cover-graphic"> <img src="https://oxfordglobal.com/hubfs/Website/Images/Resources/Discovery/Advancing%20Drug%20Discovery%20Through%20Strategic%20Collaboration.jpg" class="cover-graphic-image"> </div> </a><div class="content"><a href="/discovery-development/resources/sponsored/case-studies/ardigen/advancing-drug-discovery-through-innovative-technologies-strategic-collaboration"> <h4> Advancing Drug Discovery Through Innovative 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The Application of RNAi Therapeutics for Cardiovascular Disease Treatment