A team from University Hospitals and Case Western Reserve University has identified a small-molecule drug that effectively reduces cholesterol by 70% in animal models.
PCSK9 inhibitors are the second most common type of medication used to manage cholesterol levels, following statins. These drugs are highly effective at reducing excess cholesterol in the blood, but unlike statins, which can be taken orally, PCSK9 inhibitors must be injected. This can be a barrier to their use for some people.
A small-molecule drug that can be taken orally has been developed by researchers at University Hospitals and Case Western Reserve University School of Medicine. The drug has been shown to significantly reduce PCSK9 levels and lower cholesterol by 70% in animal models. These findings, published in the journal Cell Reports, represent a new approach to managing cholesterol and may also have implications for cancer treatments.
“Cholesterol lowering is one of the most important therapies we have to prolong life and protect people from heart disease, which is still the number one cause of morbidity and mortality in the Western world,” said Jonathan S. Stamler, MD, senior author, President, Harrington Discovery Institute at UH, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation, and Professor of Medicine and Biochemistry at UH and Case Western Reserve School of Medicine.
“Statins only lower cholesterol so far. This is a drug class that we think would represent a new way to lower cholesterol, a new way to hit PCSK9.”
Study Findings
Central to cholesterol regulation are LDL receptors, which sit at the surface of liver cells and remove cholesterol from the blood, thereby lowering serum levels. PCSK9 in the bloodstream controls the number of LDL receptors by marking them for degradation. Therefore, agents that inhibit PCSK9 increase the number of LDL receptors that remove cholesterol.
Nitric oxide is a molecule that is known to prevent heart attacks by dilating blood vessels. In the new study, Stamler and colleagues show that nitric oxide can also target and inhibit PCSK9, thus lowering cholesterol. They identify a small molecule drug that functions to increase nitric oxide inactivation of PCSK9. Mice treated with the drug display a 70% reduction in LDL “bad” cholesterol.
Beyond Cholesterol to Cancer
In addition to impacting the field of cholesterol metabolism, the findings may impact patients with cancer, as emerging evidence suggests targeting PCSK9 can improve the efficacy of cancer immunotherapies.
“PCSK9 not only targets LDL receptors for degradation, but it also mediates the degradation of MHC 1 on lymphocytes, which is used for recognition of cancer cells,” said Stamler. “PCSK9 is effectively preventing your lymphocytes from recognizing cancer cells. So, if you inhibit PCSK9, you can boost the body’s cancer surveillance. There may be an opportunity one day to apply these new drugs to that need.”
Reference: “A multienzyme S-nitrosylation cascade regulates cholesterol homeostasis” by Colin T. Stomberski, Nicholas M. Venetos, Hua-Lin Zhou, Zhaoxia Qian, Bryce R. Collison, Seth J. Field, Richard T. Premont and Jonathan S. Stamler, 25 October 2022, Cell Reports.
DOI: 10.1016/j.celrep.2022.111538
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40 Comments
Is the PCSK9 oral drug currently available? Under what name?
This is hopefully my answer for help since I cannot take statins.
The “new oral drug” has not been tested in people yet, and won’t be available for years, if ever. There is an injectible Pcsk9 drug available – “alirocumab injection,” sold as PRALUENT.
The oral drug is not available but, another is available as an injection called Rapatha.
Unfortunately, Raphata is very expensive.
I also could not tolerate statins. I went through 3 different ones. I inherited my mothers gene of high cholesterol. I had horrible leg cramps and body pain. My doctor suggested taking CoQ10 with the statin for a month. After 2 days, it worked. After 8 years, I continue to take CoQ10 for the other health benefits it provides. Hope this helps.
I would like to know as well if this PCSK9 is available because I have struggled with high cholesterol for years and have been 2 different shots that my cholesterol Dr. Has tried now I’m trying Crestor again and watching my diet,but they say it’s hereditary So PLEASE let this be available it could be the answer to my Prayers…
Dont be stupid. There IS No Drug available called Pcsk9. Pcsk9 IS Made in your Body. They are now looking for ways to Block it’s effect. But unil now there has been found only one orally usefull. And IT has Not been subjected to any clinical trials. So unfortunally there IS No Pcsk9 Inhibitor available!
Also, another called Rapatha.
Actually there is an injectible Pcsk9 drug available – “alirocumab injection,” sold as PRALUENT.
Well – people are asking – is it available?
Seems there is no answer . Why not?
.
The “new oral drug” has not been tested in people yet, and won’t be available for years, if ever. There is an injectible Pcsk9 drug available – “alirocumab injection,” sold as PRALUENT.
It takes many years of testing to generate enough data to convince the FDA (US Food and Drug Administration) and/or the EMA (European Medicines Agency) that a drug is safe and effective enough to be approved for use in humans. The drug that is the subject of this report has not been tested in humans yet, so it will be many years before testing can be completed, unless the drug is found to be unsafe right away.
I also would like to know if PCSK9 is available.
I’m interested in the new PCSK9 treatment to lower cholesterol. Nothing else seems to work.
Would like to be in clinical trials
I have very high LDL driven by my cancer drug treatment which is a side affect
It was under control with stains until a massive jump
I also would like to know when PCSK9 is available
Is this newer drug PCSK9 AVAILABLE IN THE SAN ANTONIO TEXAS AREA? WILLING TO TRY IT OUT. PLEASE ADVICE.
Can i order Pcsk9, i live in South Africa.
Is the Pcsk9 available in the UK as I have high cholesterol for many years thanks to my mom.
NAME OF DRUG PLEASE???? PLEASE?????
Will it be available anytime soon in Canada?
I can’t take stations, my cholesterol is always high. I like to participate in research if available.
Now if only cholestral actually was an indicator of heart disease. It isn’t.
We need cholesterol to live longer. There is scientific evidence both types get trigs in order eat low carb where can.
Why is cholesterol reduction important if people with low cholesterol die at rate 8x higher then people with high cholesterol? https://www.youtube.com/watch?v=aAC9xCinLnk&t=51s&ab_channel=Dr.StenEkberg
I’ve been on 5 different cholesterol drugs and none have worked.
Plus I Stopped taking the pills years ago, first heart attack was when i was 38 yrs of age, and this month i will be 69 years.
I’m currently drinking a drink I miss you of lemon garlic and ginger blended together you bring it to a boil and let it cool and you strain it put it in refrigerator and drink a glass every morning I’ll know in a couple of months if it works studies have shown it works if you’d like to try it just Google it
Hi Randy, I had high cholesterol levels a few years ago, it was suggested that I eat an Avocado every day so I did,half with breakfast and half with evening meal,my cholesterol level now about 2.5 – 3.
Pcsk9 is not the drug, it is the TARGET of the drug. The “new oral drug” has not been tested in people yet, and won’t be available for years, if ever. There is an injectible Pcsk9 drug available – “alirocumab injection,” sold as PRALUENT.
Ezetimibe has worked much better than statins for me.
For Statin intolerant patients, there is a new oral drug available in the market now. Its called Nexletol or bempedoic acid. Ask your doctor about it. PCSK9 inhibitors are effective but very expensive. It is given as an injection every 4-6 months and costs $ 150000 per year.
What is the side effects of Praluent the injectable?
The most common side effects of PRALUENT include: redness, itching, swelling, or pain/tenderness at the injection site, symptoms of the common cold, and flu or flu-like symptoms.
PRALUENT can cause serious side effects, including allergic reactions that can be severe and require treatment in a hospital. Stop using PRALUENT and call your healthcare provider or go to the nearest hospital emergency room right away if you have any symptoms of an allergic reaction including a severe rash, redness, hives, severe itching, trouble breathing or swelling of the face, lips, throat, or tongue.
Don’t be stupid and avoid intake of regular medicine..exercise regulalrly and avoid esting cholestrol rich food.medicine have so many side effects.
To bring down your cholesterol just a couple servings of oat meal (should be steel cut oats and not the regular instant type) every week and interspersed that with a couple servings of lentil. They will bring down your number with no need for prescription drugs. It would also help tremendously to eat more green leafy vegetables. The more colorful the vegetables,the more natural vitamins and antioxidants you will have.
Asking a question is never stupid, yet, “DON’T BE STUPID” is a very stupid response!
If you read the article it explains that the drug is a PCSK9 inhibitor, it is not the name of the drug
There’s a product i have taken in New Zealand called:
GO healthy
GO Cholesterol Shield, statin support,
you don’t need to be taking statins to take this
It’s Plant Sterols with Co-Q10 & Lecithin, in Capsule form, take one a day to control cholesterol, two a day too lower Cholesterol, it works very well in reducing Cholesterol. You can also purchase Plant Sterols in tablet form, Plant Sterols reduce cholesterol.
After I discovered that I have a cholesterol according the doctor’s findings from my blood. Because I was suffering from sharp pain the whole day.
Oh watch big pharma jack the price of this drug up to point where even the Billionaires won’t want to afford it. Wait 20 years (after the patent expires), then you might have a shot of affording this drug.