siRNAs for cardiovascular disease?! 🧬 I recently studied up on this and wanted to share some of my most salient notes. 📝 20% of the population has elevated lipoprotein A levels - Lp(a), which presents a risk factor for cardiovascular problems. Lp(a) is plaque forming, and it makes problematic types of lipid carriers, which are similar to but different than #LDL-cholesterol. ⚕️It is now suggested that a good majority of atherosclerotic cardiovascular disease is not driven by LDL-cholesterol but instead genetically elevated Lp(a), which cannot be modified much by adapting diet and exercise. 📉 #Lepodisiran from Eli Lilly and Company #Olpasiran from Amgen, and #Zerlasiran from Silence Therapeutics plc have shown impressive clinical results to give long duration reductions in LpA levels. Each uses #GalNAc conjugates for efficient uptake by the liver. The molecular design of each is unique, though. I’ve compiled some of my #siRNA pharmacology and molecular structure notes in the attached Figure. Perhaps this wave of pipeline success and molecular design will intrigue you too. Olpasiran (Amgen): Phase 3 started Dec 2022. Lepodisiran (Lilly): Phase 3 started Mar 2024. Zerlasiran (Silence): Phase 2 ending soon. 📊Efficacy + Dosing Durability: https://lnkd.in/ekxMHbfe #biotech #CGT #GTx #oligonucleotides #PKPD #ADME #HPLC #LCMS ————————— I’m Matt Lauber - an analytical biochemist who loves separating biomolecules, detecting masses, and all things biotechnology! ☑️ Follow & subscribe 🔔
Ashish A, Kanhed
3mo
Thank you for sharing this! The way you've explained the new siRNA therapies targeting lipoprotein(a) is so clear and informative. appreciate the breakdown of each drug especially in terms of dosing and effectiveness. It's exciting to see these advancements in cardiovascular care, and your post makes it easy to understand. I will also like to know about what analytical techniques do you use to evaluate the structure, purity, and stability of siRNA-based molecules during drug development?
Very informative. Thank you for sharing.
Ansie Martin
3mo
siRNA treatments are most impactful on diseases with a genetic component and that have the least impact by a lifestyle change. Among the genetic predisposition to atherosclerotic cardiovascular diseases in particular, overexpression of lipoprotein a is definitely a major factor. This is a good example of personalised treatment. Amazing share Matthew Lauber 🙂👌
Theo Van Berkel
3mo
I am happy to see that the GalNAc targeting system is working so nice and efficient.
Joe Fredette
3mo
Great post Matt! Thanks for sharing. So much has been written about the promise of oligonucleotide therapeutics for rare diseases, which is fantastic, but cardiovascular disease is definitely not rare! It will be very interesting to see the results from these trials.
Rebecca Miles
3mo
Cool
Biotech/Pharma/Devices/Education Professional
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