Here's the crux of it. Non-HDL-C, ApoB, TRL-C(triglyceride rich lipoprotein) and ApoC3. 20-26% reduction in ApoB & non-HDL-C is approaching moderate intensity statin reduction. ApoC3 decrease matches the drop in TRL-C(they move together) Basically a large scale clear out of atherogenic particles!
August 30, 2026 at 3:08 PM
Here's the crux of it. Non-HDL-C, ApoB, TRL-C(triglyceride rich lipoprotein) and ApoC3. 20-26% reduction in ApoB & non-HDL-C is approaching moderate intensity statin reduction. ApoC3 decrease matches the drop in TRL-C(they move together) Basically a large scale clear out of atherogenic particles!
This will end up as a long form blog post eventually but it's remarkable that this one drug acts on multiple drug-able targets(HMG-COA, ApoC3, ANGPTL3/8) by itself to lower lipids in addition to all its other benefits.
Full 80 week retatrutide obesity data will be revealed in 45 days!
I want to highlight a couple things besides weight loss from phase 2 that were shocking at the time and will be MORE shocking in phase 3 data.
For my cardiology & lipid nerds this thread is for you!
1/
I want to highlight a couple things besides weight loss from phase 2 that were shocking at the time and will be MORE shocking in phase 3 data.
For my cardiology & lipid nerds this thread is for you!
1/
April 23, 2026 at 12:51 PM
This will end up as a long form blog post eventually but it's remarkable that this one drug acts on multiple drug-able targets(HMG-COA, ApoC3, ANGPTL3/8) by itself to lower lipids in addition to all its other benefits.
In studies of metabolically healthy/unhealthy #obesity APOC3 was identified as a novel predictor for obesity stratification www.medrxiv.org/content/10.1...
March 23, 2025 at 1:58 AM
In studies of metabolically healthy/unhealthy #obesity APOC3 was identified as a novel predictor for obesity stratification www.medrxiv.org/content/10.1...
Discover a long-acting siRNA targeting APOC3 to lower triglycerides and combat hypertriglyceridemia risks, including pancreatitis. PMID:41163544, Nucleic Acids Res 2025, @NAR_Open @OTSociety @NAR_Open https://doi.org/10.1093/nar/gkaf1063 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
https://doi.org/10.1093/nar/gkaf1063
No description available
doi.org
December 16, 2025 at 3:10 AM
And before someone says this is weight loss mediated, 1.) it's not. 2.) because weight loss was similar between the two drugs despite Reta being a shorter trial 3.) because glucagon is lipolytic & 4.) there's some deep mechanisms at play here. Enter ApoC3 and ANGPTL 3/8
April 22, 2026 at 3:57 PM
And before someone says this is weight loss mediated, 1.) it's not. 2.) because weight loss was similar between the two drugs despite Reta being a shorter trial 3.) because glucagon is lipolytic & 4.) there's some deep mechanisms at play here. Enter ApoC3 and ANGPTL 3/8
That leads to the other calling Reta what it is, at minimum a moderate intensity statin drug. That's fun since it was designed for weight loss and diabetic control!
As noted it also functions like drugs from other lipid lowering therapeutics namely fibrates, ApoC3 and ANGPTL3 inhibitors
As noted it also functions like drugs from other lipid lowering therapeutics namely fibrates, ApoC3 and ANGPTL3 inhibitors
August 30, 2026 at 3:08 PM
That leads to the other calling Reta what it is, at minimum a moderate intensity statin drug. That's fun since it was designed for weight loss and diabetic control!
As noted it also functions like drugs from other lipid lowering therapeutics namely fibrates, ApoC3 and ANGPTL3 inhibitors
As noted it also functions like drugs from other lipid lowering therapeutics namely fibrates, ApoC3 and ANGPTL3 inhibitors
Broadly oversimplifying here but blocking both things reduce triglycerides, but ANGPTL 3/8 reduces LDL cholesterol and ApoC3 reduces TRL-C(Triglyceride rich lipoprotein cholesterol) or "remnant cholesterol" too
That's visualized in these slides.
Both LDL and TRL are considered highly atherogenic.
That's visualized in these slides.
Both LDL and TRL are considered highly atherogenic.
April 22, 2026 at 3:57 PM
Broadly oversimplifying here but blocking both things reduce triglycerides, but ANGPTL 3/8 reduces LDL cholesterol and ApoC3 reduces TRL-C(Triglyceride rich lipoprotein cholesterol) or "remnant cholesterol" too
That's visualized in these slides.
Both LDL and TRL are considered highly atherogenic.
That's visualized in these slides.
Both LDL and TRL are considered highly atherogenic.
In another home-run for genetics-enabled drug development, APOC3 inhibition is approved to treat a disease of hypertriglyceridemia.
👇
www.science.org/doi/10.1126/....
Human genetics identified the target in 2008, thanks to work done in the Amish population.
👇
www.nature.com/articles/s41...
👇
www.science.org/doi/10.1126/....
Human genetics identified the target in 2008, thanks to work done in the Amish population.
👇
www.nature.com/articles/s41...
A Null Mutation in Human APOC3 Confers a Favorable Plasma Lipid Profile and Apparent Cardioprotection
Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancast...
www.science.org
January 21, 2025 at 12:14 AM
In another home-run for genetics-enabled drug development, APOC3 inhibition is approved to treat a disease of hypertriglyceridemia.
👇
www.science.org/doi/10.1126/....
Human genetics identified the target in 2008, thanks to work done in the Amish population.
👇
www.nature.com/articles/s41...
👇
www.science.org/doi/10.1126/....
Human genetics identified the target in 2008, thanks to work done in the Amish population.
👇
www.nature.com/articles/s41...
@nationallipid.bsky.social #NLASession Dr. Gaudet describing the various APOC3 inhibitors
May 30, 2025 at 1:59 PM
@nationallipid.bsky.social #NLASession Dr. Gaudet describing the various APOC3 inhibitors
First Gene-Editing Therapy Targeting APOC3 Marks a Milestone for Hyperlipidemia Treatment#China#Shanghai#CorrectSequence#Hyperlipidemia#APOC3
First Gene-Editing Therapy Targeting APOC3 Marks a Milestone for Hyperlipidemia Treatment
CorrectSequence Therapeutics has achieved a groundbreaking milestone by successfully administering the first-ever gene-editing therapy targeting APOC3 for hyperlipidemia patients. This innovation could mean a significant shift in treatment protocols.
third-news.com
November 7, 2025 at 1:56 PM
First Gene-Editing Therapy Targeting APOC3 Marks a Milestone for Hyperlipidemia Treatment#China#Shanghai#CorrectSequence#Hyperlipidemia#APOC3
Groundbreaking Gene Editing Therapy Targets APOC3 to Address Hyperlipidemia#China#Shanghai#gene_therapy#CorrectSequence#Hyperlipidemia
Groundbreaking Gene Editing Therapy Targets APOC3 to Address Hyperlipidemia
CorrectSequence Therapeutics has unveiled the first gene editing treatment targeting APOC3 to combat hyperlipidemia, marking a major milestone in medical biotechnology.
third-news.com
November 9, 2025 at 8:04 AM
Groundbreaking Gene Editing Therapy Targets APOC3 to Address Hyperlipidemia#China#Shanghai#gene_therapy#CorrectSequence#Hyperlipidemia
Two streams in a row? That's a first 👀 I'm gonna continue on some #Phasmophobia to get that practice for the Apoc3 challenge... we're still on the Ranger Challenge... Time for spooks! 👻
💙 twitch.tv/hylifoxx
💙 twitch.tv/hylifoxx
March 9, 2025 at 6:09 PM
Two streams in a row? That's a first 👀 I'm gonna continue on some #Phasmophobia to get that practice for the Apoc3 challenge... we're still on the Ranger Challenge... Time for spooks! 👻
💙 twitch.tv/hylifoxx
💙 twitch.tv/hylifoxx
Gynxz - Live on Twitch
Phas Rollover challenge Insanity-Apoc3 / !bingo / !phas | Streaming phasmophobia.
www.twitch.tv
September 11, 2026 at 10:08 PM
Tedavi ayrıca, normalde bu parçalanmayı yavaşlatan iki protein olan ApoC3 ve ANGPTL3'ün aktivitesini azaltarak trigliseridlerin parçalanmasını hızlandırdı.
January 18, 2026 at 7:03 PM
Tedavi ayrıca, normalde bu parçalanmayı yavaşlatan iki protein olan ApoC3 ve ANGPTL3'ün aktivitesini azaltarak trigliseridlerin parçalanmasını hızlandırdı.
Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia | New England Journal of Medicine www.nejm.org/doi/full/10....
Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia | NEJM
Highly effective therapies to reduce triglyceride levels are lacking. Olezarsen is
an N-acetylgalactosamine–conjugated antisense oligonucleotide that targets the messenger
RNA of apolipoprotein C-I...
www.nejm.org
October 6, 2025 at 8:23 PM
Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia | New England Journal of Medicine www.nejm.org/doi/full/10....
August 10, 2025 at 8:02 PM
World's First Gene-Editing Therapy for Hyperlipidemia Approved#China#Shanghai#Gene_Editing#CorrectSequence#APOC3
World's First Gene-Editing Therapy for Hyperlipidemia Approved
CorrectSequence Therapeutics announces a groundbreaking gene-editing treatment targeting APOC3 for hyperlipidemia, marking a significant medical milestone.
third-news.com
November 7, 2025 at 1:40 PM
World's First Gene-Editing Therapy for Hyperlipidemia Approved#China#Shanghai#Gene_Editing#CorrectSequence#APOC3
LDL-cholesterol is in the causal chain for atherosclerosis. It looks like there is residual risk that LDL-c doesn't explain, and other lipid entities are appealing candidates.
Enter olezarsen, which degrades APOC3 mRNA and reduces ApoC-III levels. This lowers TG & remnant cholesterol.
Enter olezarsen, which degrades APOC3 mRNA and reduces ApoC-III levels. This lowers TG & remnant cholesterol.
Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk | NEJM
Patients with severe hypertriglyceridemia have an increased risk of acute pancreatitis.
The efficacy and safety of olezarsen, an antisense oligonucleotide targeting apolipoprotein
C-III messenger R...
www.nejm.org
April 1, 2026 at 7:14 PM
LDL-cholesterol is in the causal chain for atherosclerosis. It looks like there is residual risk that LDL-c doesn't explain, and other lipid entities are appealing candidates.
Enter olezarsen, which degrades APOC3 mRNA and reduces ApoC-III levels. This lowers TG & remnant cholesterol.
Enter olezarsen, which degrades APOC3 mRNA and reduces ApoC-III levels. This lowers TG & remnant cholesterol.
Yesterday when I was attempting Apoc 3 again at Sunny Meadows on Phasmophobia...
Got a Blood Moon on the day of the actual Blood Moon... 🥴
Instant reset...
#phasmophobia #apoc3 #bloodmoon
Got a Blood Moon on the day of the actual Blood Moon... 🥴
Instant reset...
#phasmophobia #apoc3 #bloodmoon
March 14, 2025 at 7:28 PM
Yesterday when I was attempting Apoc 3 again at Sunny Meadows on Phasmophobia...
Got a Blood Moon on the day of the actual Blood Moon... 🥴
Instant reset...
#phasmophobia #apoc3 #bloodmoon
Got a Blood Moon on the day of the actual Blood Moon... 🥴
Instant reset...
#phasmophobia #apoc3 #bloodmoon
Ich bin nun Live auf Twitch! Ich Spiele Phasmophobia auf https://www.twitch.tv/qu4rtor . Ich würde mich freuen wenn du Einschalten würdest!
Qu4rtor - Twitch
[GER] Wir versuchen uns an der Apoc3 Challenge! #01-25
www.twitch.tv
January 26, 2025 at 2:01 PM
Ich bin nun Live auf Twitch! Ich Spiele Phasmophobia auf https://www.twitch.tv/qu4rtor . Ich würde mich freuen wenn du Einschalten würdest!
STEAP3 variation also mapped to several apolipoproteins (including APOA1, APOC3, APOE), linking RBC iron handling to lipid oxidation and vesiculation pathways, potentially bridging neurodegenerative disease biology to RBC iron metabolism with systemic oxidative stress.
November 19, 2025 at 8:24 PM
STEAP3 variation also mapped to several apolipoproteins (including APOA1, APOC3, APOE), linking RBC iron handling to lipid oxidation and vesiculation pathways, potentially bridging neurodegenerative disease biology to RBC iron metabolism with systemic oxidative stress.
Great review of the evolving landscape of therapeutics targeting triglycerides & remnant cholesterol.
Human genetics has been key to shaping this field with discoveries of loss-of-function variants in APOC3, ANGPTL3, ANGPTL4 having directly triggered clinical development 🧬-->💊
Human genetics has been key to shaping this field with discoveries of loss-of-function variants in APOC3, ANGPTL3, ANGPTL4 having directly triggered clinical development 🧬-->💊
May 14, 2025 at 1:12 PM
Great review of the evolving landscape of therapeutics targeting triglycerides & remnant cholesterol.
Human genetics has been key to shaping this field with discoveries of loss-of-function variants in APOC3, ANGPTL3, ANGPTL4 having directly triggered clinical development 🧬-->💊
Human genetics has been key to shaping this field with discoveries of loss-of-function variants in APOC3, ANGPTL3, ANGPTL4 having directly triggered clinical development 🧬-->💊
New study: A hepatic-targeted APOC3 antisense oligonucleotide shows promise in treating familial chylomicronemia syndrome.
🔬 The paper dives into key clinical considerations and potential benefits for patient care.
🔗 https://ow.ly/LrsK50XtAEW
#LipidDisorders #GeneTherapy #CardioSky #MedSky
🔬 The paper dives into key clinical considerations and potential benefits for patient care.
🔗 https://ow.ly/LrsK50XtAEW
#LipidDisorders #GeneTherapy #CardioSky #MedSky
November 18, 2025 at 4:36 PM
New study: A hepatic-targeted APOC3 antisense oligonucleotide shows promise in treating familial chylomicronemia syndrome.
🔬 The paper dives into key clinical considerations and potential benefits for patient care.
🔗 https://ow.ly/LrsK50XtAEW
#LipidDisorders #GeneTherapy #CardioSky #MedSky
🔬 The paper dives into key clinical considerations and potential benefits for patient care.
🔗 https://ow.ly/LrsK50XtAEW
#LipidDisorders #GeneTherapy #CardioSky #MedSky