Injection Could Slash Heart Attack Risk By 90% (But It Isn't Available Just Yet)

Could This See Heart Attacks Decrease?
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A single injection that slashes heart attack risk by up to 90% could be available within 10 years, say scientists.

The jab, that only has to be administered once, has already been tested successfully on mice.

It uses cutting-edge DNA-editing technology to "knock out" a liver gene linked to raised levels of cholesterol in the bloodstream.

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In the laboratory mice, the injection reduced blood concentrations of cholesterol by 35% to 40% within days. A similar impact on cholesterol in humans would lower the risk of heart attacks by as much as 90%.

US lead scientist Dr Kiran Musunuru, from the Harvard Stem Cell Institute (HSCI), said: "Heart attack is the leading natural killer worldwide, with one in two men and one in three women past the age of 40 having heart attacks in their lifetimes.

"If you had a therapy that targeted the liver, changed the genome - and if it were totally safe - then at least in theory you could think of this therapy as something like a vaccination.

"It could be a one-time treatment, a permanent alteration. If you used this in a population, you could reduce the occurrence of heart attack by 30%, 50%, 90%."

He said although the research was at a very early stage, the first trial patients could be offered the treatment within a decade.

The jab targets a liver gene called PCSK9 which is known to regulate levels of harmful cholesterol, or low-density lipoprotein (LDL).

In 2003, a team of French scientists found that people who inherited very high cholesterol levels and a vulnerability to early heart attacks carried a rare super-active variant of the gene.

Heart Attack Signs You Might Be Ignoring...
Heart Attack Symptoms You're Likely To Ignore(01 of07)
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(credit:Alamy)
Burning Pain In Abdomen(02 of07)
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"A dull ache or burning sensation in the epigastrum (upper part of the abdomen). Not all pain typically occurs in the centre of the chest," explains Dr Sanjay Sharma. "The blockage in the heart could cause symptoms similar to indigestion (like fullness, bloating and problems swallowing). If these symptoms longer than two days, seek medical advice." (credit:Alamy)
Aching Neck And Jaw (03 of07)
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"Severe pain or pressure sensation around the jaw and neck only could be a sign," says Dr Sanjay Sharma. "If it starts off as a mild discomfort but gradually worsens, seek medical advice immediately." (credit:Alamy)
Upper Back Pain(04 of07)
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"Pain in the centre of the upper back is often mistaken for muscular pain, but could be a 'silent heart attack' symptom," says Dr. Sanjay Sharma."If in doubt, speak to a medical professional as soon as possible." (credit:Alamy)
Breathlessness(05 of07)
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"Being suddenly short of breath, without any chest pain could be a sign of a herat attack - although it's more likely to occur in elderly people or diabetics. The chest pain could be due to the lack of oxygen to the heart muscle," says Dr Sanjay Sharma. "The breathlessness is often due to the fact that the heart is no longer pumping properly causing the lungs to fill up with fluid." (credit:Alamy)
Dizziness And Sweating(06 of07)
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Dizziness and sweating is a common sign," says Dr Sanjay Sharma. "The sweating is a normal reaction to severe pain and the loss of consciousness may be due to a drop in blood pressure the heart going into a very slow, or very fast electrical rhythm, due to the effects of lack of oxygen." (credit:Alamy)
'Pulled Muscle'(07 of07)
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"If chest pain spreads to your left or right arm, that could be another sign you're having a heart attack. We've heard from heart attack survivors who thought they'd pulled a muscle and waited until the following day before getting themselves to hospital," adds Ellen Mason, senior cardiac nurse from the British Heart Foundation. (credit:Alamy)

Then a Texan group discovered that about 3% of the general population possess PCSK9 mutations that have the opposite effect. They have LDL levels some 15% to 28% lower than average, and a 47% to 88% reduced heart attack risk.

"Our reasoning was that nature has already done the experiment; you have people who have won the genetic lottery," said Dr Musunuru.

"They are protected from heart attack, and there are no known adverse consequences. So that led us to reason that if we could find a way to replicate this, we could significantly protect people from heart attack."

Advances in gene-editing technology provided the solution in the form of a tool called CRISPR/Cas9, discovered in 2007, which allows scientists to home in on and erase specific DNA sequences.

CRISPR/Cas9 makes it far easier to disrupt or "knock out" chosen genes in the course of scientific research.

Dr Musunuru's team found they could prime the gene-editing tool to target PCSK9 in the liver and deliver it via a single injection.

"The PCSK9 gene is expressed primarily in the liver, and produces a protein that is active in the bloodstream and prevents the removal of cholesterol from the blood," said the scientist.

"Several drug companies have been developing antibodies to it, but the problem with antibody-based drugs is they don't last forever; you'd need an injection every few weeks.

"The main option for reducing cholesterol is statin drugs, such as Lipitor, but many people taking statin drugs every day still have heart attacks. So there is still a great need for other approaches."

He added: "The first question was whether we could get CRISPR/Cas9 into the liver, and once we got it into the liver, would it function properly? And it did. It could have had no effect, but it turned out to have a dramatic effect.

"Within three to four days of delivering the system into the liver, the majority of the PCSK9 gene copies in all of the liver cells were disrupted, knocked out. And what we hoped to see was much less of the protein product in the bloodstream, which is what we saw.

"The other consequence that we saw was a 35% to 40% reduction in cholesterol levels in these mice, which would translate in humans to a heart attack risk-reduction of as high as 90%."

The findings are reported in the American Heart Association journal Circulation Research.