Stopping Heart Attacks

**tomcat** · 14-05-2022, 04:00 PM

Putting an End to Heart Attacks by Editing Human DNA

Verve Therapeutics is targeting cholesterol-causing genes to clear arteries with its experimental therapy.

By Angelica Peebles

May 6, 2022, 5:00 PM GMT+7

Even after decades of drug breakthroughs aimed at preventing heart attacks, they remain the world’s leading cause of death. The pills and injections on the market do the job of lowering the cholesterol that clogs blood vessels and puts people at risk of a heart attack. But not everyone has access to them, and some won’t stick to treatment plans that can last the rest of their lives. Verve Therapeutics Inc. is proposing a radical solution: altering a person’s genome—the body’s instruction manual—to stop the buildup of bad cholesterol. “We’re on the cusp of potentially transforming that model to a one-and-done treatment,” says Sekar Kathiresan, chief executive officer of the Cambridge, Mass.-based company.

Verve plans to initially target those who’ve already had a heart attack because of extremely high cholesterol caused by a hereditary condition known as familial hypercholesterolemia, which affects 31 million people globally. If it works to reduce low-density lipoprotein (LDL), or “bad,” cholesterol in that group, the company would look to widen the treatment pool, eventually aiming to give it to young people as a preventive measure, though it’s too early to say when that could happen.

The company is backed by Google Ventures (now known as GV) and prominent biotech investors Arch Venture Partners and F-Prime Capital. It went public in June, reaching a market capitalization of $2.89 billion that month. (Its value has since dropped to about $700 million, falling along with the rest of the biotech sector.)

Kathiresan helped found Verve when he was an acclaimed cardiologist and geneticist at Harvard, where he discovered genetic mutations that caused people to have low levels of cholesterol, offering them protection from heart attacks. Now he’s trying to replicate that phenomenon by turning off cholesterol-raising genes. Verve is developing medicines focused on two genes. The first treatment will go after PCSK9; the second will be directed at ANGPTL3. Some patients will need only one of the drugs; others will need both. The company uses the Crispr DNA-editing tool to change a single letter of a person’s genome. A lipid nanoparticle encases the editing system to protect it on its journey to the liver, where it turns off the desired gene.

The treatment showed encouraging signs in monkeys, cutting bad cholesterol levels by 59% after two weeks and sustaining the effect six months later. Verve is set to begin testing in humans within months; it will then be years before it has enough evidence of the drug’s safety and efficacy to consider seeking approval from regulators.

Verve will face plenty of hurdles in its attempt to treat the masses. It’s one of the first tests of using Crispr to edit DNA inside the human body, and patients and doctors could be wary of making a permanent change without knowing much about long-term safety, says Elizabeth McNally, director of the Center for Genetic Medicine at the Northwestern University Feinberg School of Medicine. Reluctance to take Covid-19 vaccines suggests some people may be loath to alter their DNA, she says.

Even if Verve can prove the drug is safe and effective at slashing levels of bad cholesterol in humans, it will then need to convince insurers it’s worth covering when it will almost certainly be more expensive than other available options, says Michael Sherman, chief medical officer at Point32Health Inc., a health insurance company based in Canton, Mass. “There has to be a reason to do the gene therapy to allow it, as opposed to it’s just newer and cooler,” he says.

Statins, the pills that became available some 35 years ago to reduce cholesterol, now cost as little as $9 for a month’s supply. The self-injectable medicines that emerged a few years ago, known as PCSK9 inhibitors—while better at lowering cholesterol than statins and requiring administration only every few weeks—haven’t reached many patients in part because they cost thousands of dollars a year. Amgen Inc. and Regeneron Pharmaceuticals Inc., the makers of the injections, haven’t been able to sway insurers even when targeting the highest-risk people with familial hypercholesterolemia, despite cutting prices by more than half, to $6,000 a year. Also, some people are wary of administering self-injections.

So far, analysts forecast that Verve’s therapy will cost from $50,000 to $200,000 per patient. Companies rarely reveal much about pricing before their products hit the market, but Kathiresan says the estimated range is “a reasonable starting point.”

Kathiresan says millions of people don’t take advantage of existing treatments and an infusion given to a young person could fundamentally alter their risk for the rest of their lives. It’s something that might have helped his own brother, who unexpectedly died of a heart attack at age 42. “What excites me is this is the answer to heart attack,” Kathiresan says. “If it works.”

**pickel** · 15-05-2022, 12:46 AM

I would get it. I've just been diagnosed with high cholesterol and extremely high triglycerides. A statin has been prescribed but I want to try changing my diet and exercising more first. But the frustration of reading food labels and having to put the product back on the shelf is pissing me off, so I may end up taking them. The doc figures it might be genetic, so I might not have a choice.

**Troy** · 15-05-2022, 03:17 PM

^ I had similar problems with cholesterol and high triglycerides. I agree about the food labelling and spend a lot of time trying to find low fat and low sugar products. The worst is when supermarkets sell certain brands for a few months and then switch to own brands with similar packaging but much higher levels of sugar/fat. Just plain fraud in my opinion.

Anyway, I cut both my cholesterol and triglyceride levels by exercising on average 1 hour per day. Nothing strenuous, just a 20 minute walk before and after work (I park my car a mile away and walk in) and a 30-40 minute walk during my lunch break. That alone made a huge difference to the levels.

If you can mange it then stop drinking altogether. I'm not ready for such a drastic step, but I abstain for 3-4 weeks at a time and then have a few beers. Wine is limited to a bottle a month, which allows me to sample some of the better ones.

**tomcat** · 15-05-2022, 03:27 PM

Originally Posted by Troy

Anyway, I cut both my cholesterol and triglyceride levels by exercising on average 1 hour per day

...I do that as well...5:15-6:15 every morning...I also cut out all beef. Result: cholesterol levels around 130-140 for the last 20 years...cutting down on my moderate drinking is next-level restraint and may not even be necessary...fingers crossed...

**pickel** · 15-05-2022, 11:20 PM

I've switched from beer to red wine, and have 1-3 glasses most days, but not every day. Been trying to go for long walks but it's been pissing rain here most days lately. Every couple of days I take the stairs to my apartment on the 11th floor, as well.

What bothers me is the amount of conflicting information available about what is good or bad for cholesterol. It's doing my head in and part of me wants to give up trying to manage my food intake, and eat what I want. I really don't think I have an unhealthy diet. Ice cream and bacon were probably the worst culprits, though i didnt really eat a lot, so I've stopped those. I don't eat a lot of sugary stuff, and very rarely any processed foods. I've incorporated a lot more healthy salads into my diet, but am getting bored of that as well.

**Joe 90** · 15-05-2022, 11:29 PM

Originally Posted by Troy

If you can mange it then stop drinking altogether. I'm not ready for such a drastic step

Me neither!
It's the only thing that keeps me sane

Half an Aspirin a day and plenty of water and exercise should keep a potential heart attack at bay.

**Storekeeper** · 16-05-2022, 01:31 AM

Retiring and moving back to Thailand is my plan to stop a heart attack. My plan is simple … cut out the junk food, get my fat arse moving and hopefully cut out the smokes.

**Joe 90** · 16-05-2022, 02:28 AM

Originally Posted by Storekeeper

hopefully cut out the smokes.

That's the hard part mate,!

Maybe cut down..

**pickel** · 16-05-2022, 05:35 AM

Originally Posted by Joe 90

That's the hard part mate,!

Maybe cut down..

I bought a nicotine vape yesterday to try and cut down. Makes me cough and gives me a headache.

**tomcat** · 16-05-2022, 09:30 AM

Originally Posted by Storekeeper

cut out the smokes

...yep...

Originally Posted by Joe 90

Maybe cut down..

...nope...

Originally Posted by pickel

I bought a nicotine vape

...nope...

**Troy** · 16-05-2022, 09:39 AM

^ I stopped 10 years ago, woke up on a Monday, threw remaining cartons in the bin and never smoked again. It was one of the best things I ever did.

Don't use a substitute, just stop. First couple of months were difficult but it's worth it.

**Buckaroo Banzai** · 16-05-2022, 10:42 AM

I read that only about 20% of the cholesterol in your bloodstream comes from the food you eat.
If I understand that correctly then a perfect diet would only reduce cholesterol by 20%.
I am a good weight for my height (5ft 9inch 165 lbs) , exercise regularly ,dont smoke or is a heavy drinker, and ate a low cholesterol diet,
Yet I had high cholesterol.
I now take 20 mg of Atorvastatin and keep my cholesterol at a reasonable level without having to worry about my diet. Though I do like my vegetables and I think I have a reasonably healthy diet.
I am sure my cholesterol problem is genetic, and would be interested in the above research, but I am not holding my breath that anything like that would become widely available in my lifetime.

**pickel** · 16-05-2022, 10:59 AM

^
I've read that as well. I've also read the opposite. That's what's pissing me off at the moment.

**PAG** · 16-05-2022, 11:35 AM

Originally Posted by pickel

I bought a nicotine vape yesterday to try and cut down. Makes me cough and gives me a headache.

Right after Songkran 2021, I moved from 2 or 3 packs of Marlboro a day to vaping. I actually had 3 machines so there was always one juiced up and charged. At the beginning of July, I stopped completely so in a few weeks it will be one year. A lot of pluses and minuses for using vaping as a means of stopping, but it certainly worked for me.

**Buckaroo Banzai** · 16-05-2022, 11:51 AM

Originally Posted by pickel

^
I've read that as well. I've also read the opposite. That's what's pissing me off at the moment.

Yea , I know how you feel. one day it's this , next day it's that. Eggs are bad for you, eggs are good for you . etc.
enough to drive you mad.
Sometimes I think they are actively trying to confuse us.

**Buckaroo Banzai** · 16-05-2022, 11:56 AM

Originally Posted by PAG

Right after Songkran 2021, I moved from 2 or 3 packs of Marlboro a day to vaping. I actually had 3 machines so there was always one juiced up and charged. At the beginning of July, I stopped completely so in a few weeks it will be one year. A lot of pluses and minuses for using vaping as a means of stopping, but it certainly worked for me.

Quitting was certainly was one of the toughest things I did, and one of the best.
I Used to time my commute home after work with cigarettes ,
I remember driving after I quit and thinking to myself "Now what"
Happy to say it's been 34 years now, and I never even think of them.
Hang in there , it gets easier.

Good Luck.

**pickel** · 16-05-2022, 12:20 PM

Originally Posted by PAG

A lot of pluses and minuses for using vaping as a means of stopping, but it certainly worked for me.

Did you find the vape to be harsh and make you cough? Or am I doing it wrong? I don't have a flavoured one, just nicotine.

**aging one** · 16-05-2022, 12:27 PM

How many mg of nic? You may have too strong of a vape.

**PAG** · 16-05-2022, 01:14 PM

Originally Posted by pickel

Did you find the vape to be harsh and make you cough? Or am I doing it wrong? I don't have a flavoured one, just nicotine.

Just dug out my vaping kit. I actually have 5 devices, not 3, along with boxes of spare coils.

This was the juice I used, different flavours but all high nicotine.

**aging one** · 16-05-2022, 01:17 PM

48 mg's holy shit!! I have never seen it so high. Wow. I vaped 15, 10, then 5 and basically have quit now.

**pickel** · 16-05-2022, 01:19 PM

Originally Posted by aging one

How many mg of nic? You may have too strong of a vape.

They come in pods that clip into the vape. 20mg/ml

**aging one** · 16-05-2022, 01:56 PM

I guess these new vape pens are using higher nicotine than the old gear. So yes I would say you are coughing as its too strong. As I said 15 was to much for me and I kept decreasing.

**Joe 90** · 16-05-2022, 02:59 PM

Originally Posted by PAG

2 or 3 packs of Marlboro a day to

Ruddy hell PAG that's old skool hardcore, surprised you're still with is.

I've started drinking lemon water in the morning as a preventative against heart attacks...
Ways Your Body May Benefit From Lemon
Relieves a sore throat. Warm water mixed with honey and lemon is a popular home remedy for people with sore throats. ...
Cancer-fighting benefits. ...
Prevents kidney stones. ...
Aids in digestion. ...
Helps blood sugar. ...
Promotes weight loss. ...
Helps clear skin.

**Polkadot** · 16-05-2022, 09:30 PM

Originally Posted by pickel

I would get it. I've just been diagnosed with high cholesterol and extremely high triglycerides. A statin has been prescribed but I want to try changing my diet and exercising more first. But the frustration of reading food labels and having to put the product back on the shelf is pissing me off, so I may end up taking them. The doc figures it might be genetic, so I might not have a choice.

High cholestrol people live longer according to studies. Statins are worse.

**misskit** · 16-05-2022, 09:36 PM

^ Link?

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