Irish Daily Mail

Could one jab stop you getting dementia and heart disease?

Evidence is pointing to a single bug that could be the cause of some big killers...

- By DEBORAH MACKENZIE

DEMENTIA is on the rise in Ireland, with around 4,000 people receiving a diagnosis every single day. In 2016 it was estimated that around 55,000 people were living with dementia in Ireland and this figure is set to rise to 65,000 by next year.

The rise in diagnoses is mainly due to increased life expectancy. Age is the biggest known risk factor, with roughly one in six people over 80 suffering from it.

And, while more than ever is known about the steps we can all take to reduce our risk – by stopping smoking, losing weight or doing more exercise – there is nothing that can completely prevent, cure, or effectivel­y treat it. For that, we need to know what causes it.

But despite decades of scientific research — and billions of pounds invested — there are no solid answers.

One theory for Alzheimer’s — the most common kind of dementia — is, however, rapidly gaining traction.

According to a group of scientists, mounting

evidence suggests that everyday germs are to blame. Specifical­ly, one type of bacteria most commonly found inside our mouths is increasing­ly being implicated.

Astonishin­gly, there is evidence this bug could also be responsibl­e for many of the other major health concerns of modern times: heart disease, diabetes and many types of cancer.

If these scientists are right, treating it could possibly halt the majority of Ireland’s diseases of old age —just like that.

The most promising thing, says Steve Dominy, head scientist at Cortexyme, a small San Fransciso drug developer who are attempting to develop one such treatment, is that ‘we can now explain things about the disease that until now had no explanatio­n.’

And, most tantalisin­g of all, is the possibilit­y of developing a vaccine, which equips the immune system to spot and destroy these bacteria. Indeed, one such vaccine is about to be tested in humans.

SCIENTISTS IN SEARCH OF THE MISSING LINK

A CENTURY or so ago, people used to die, mainly, of diseases caused by bacteria and viruses — tuberculos­is, cholera, typhoid and smallpox among others.

But, thanks to the advent of modern sanitation, antibiotic medication and vaccinatio­n, many of these killers are now rare in countries such as Ireland. Today, it’s our lifestyles that are often blamed for illness and ‘avoidable’ death.

In July, Harvard researcher­s, looking at health records across the world, suggested poor diet was a factor in 11million deaths, or 22 per cent of the total recorded.

The vast majority of diet-related deaths were due to heart disease, followed by cancers and type 2 diabetes. Having one of these makes developing the others more likely.

Smoking tobacco was associated with a modest eight million deaths, by comparison. Regular exercise, on the other hand, seems to have the opposite effect – and is linked to less illness and a longer life.

However, none of this is simple cause and effect: do this and you will, or won’t, get that disease.

Half of smokers develop lung cancer, but the other half don’t, and no one knows why.

Last week, a major study found that high cholestero­l from age 25 onward significan­tly raised the risk of heart attacks and stroke in later life — and taking statins to reduce levels had a protective effect.

Yet, half of those who suffer a heart attack have a ‘normal’ level of cholestero­l.

Deposits of a protein called amyloid in the brain are supposed to cause Alzheimer’s, but some with Alzheimer’s don’t have them, and — significan­tly — drugs that reduce amyloid have not improved the disease.

Genetics and age — two things we have no control over — are also implicated. But is there something else scientists have been missing?

THE COMMON FACTOR... INFLAMMATI­ON

RESEARCHER­S who study the biological mechanisms of disease – what’s actually happening inside the body when we develop one of these conditions — have known there is a common factor in all cases: inflammati­on.

Broadly speaking, inflammati­on is an immune system reaction to any kind of irritant in the body.

That irritant could be a foreign object, like a splinter in the foot, or other injury.

Or it could be bacteria, viruses or another pathogen.

Sensing these things, the body floods the area with immune system cells and other compounds. These destroy infected tissue, scoop up bacteria and turn on processes in cells that kill invaders.

The problem is usually dealt with quickly, and the inflammati­on goes.

But more recently, it has been found that inflammati­on is also seen in long-term conditions such as heart disease and dementia. Inflamed spots inside artery walls are thought to kickstart atheroscle­rosis — the process by which fatty cholestero­l builds up and hardens within the lining of the vessels.

These lesions, known as plaques, can rupture and trigger the formation of blood clots which can travel to the heart, causing a heart attack.

Or they can travel to the brain, where the blockage then causes a stroke.

Newer research suggests that this same process, occurring on a microscopi­c level, may contribute to gradual brain damage, and dementia.

But what causes the inflammati­on in the first place?

According to a growing network of internatio­nal experts, it might be triggered by a specific type of bacteria: Porphyromo­nas gingivalis, known as Pg to the researcher­s who study it.

THE GUM BUG FOUND IN CANCER TUMOURS

THE Pg bacteria is best known for causing one of our most common maladies: gum disease. There are more than 1,000 different types of bacteria in the mouth, living in balance, without causing problems.

But they form a sticky film on the teeth and if this isn’t brushed away, it can spread under the gumline, where it irritates and causes inflammati­on.

That immune reaction can destroy a bit of the gum, forming a pocket between gum and tooth with not much oxygen in it — an environmen­t in which Pg thrives. It proliferat­es, and emits chemicals that cause a few other kinds of bacteria to multiply, too. This triggers more inflammati­on, and deeper pockets to live in — and eventually the chronic infection and tooth loss of gum disease.

It’s long been known that people with gum disease are also more likely to develop Alzheimer’s, suffer heart attacks, Parkinson’s, liver and kidney disease and several cancers, including the deadly pancreatic kind.

But exactly why hasn’t been clear. Now, thanks to modern lab techniques that can spot previously invisible pockets of bacterial DNA

around the body, a plausible answer is emerging. Earlier this year, signs of Pg were found in the brains of Alzheimer’s patients.

Critics rightly asked whether the infection was a result of having dementia, rather than the cause. However, the Cortexyme researcher­s found Pg, at lower levels, in the brains of people who had not yet developed Alzheimer’s symptoms. This, they suggested, pointed to the fact that Pg enters the brain before Alzheimer’s starts, and is therefore not an effect of the disease, but a possible cause.

Pg has also been discovered inside inflamed plaques within artery walls, in arthritic joints, in the malfunctio­ning pancreas glands of diabetics, in failing livers, and in several types of tumour — mostly in the head and neck, and digestive tract.

IS IT TO BLAME FOR A HOST OF CONDITIONS?

COULD one bacteria be causing all these diseases? Animal experiment­s seem to back up the hypothesis.

Mice don’t normally carry Pg, but those ‘fed’ the bacteria developed gum disease — then diabetes, rheumatoid arthritis, atheroscle­rosis, fatty liver disease — and Alzheimer’s. In America, states that implement free dental care also see a drop in rates of heart attacks, strokes, diabetes and cancer.

‘There is a growing consensus that microbes in the mouth can affect physiology outside the mouth,’ says David Ojcius of the University of the Pacific in San Francisco, who studies the way the immune system responds to bacteria that cause gum disease.

Although studies confirmed Pg was found throughout the body, triggering inflammati­on — as it does in the mouth —scientists were still baffled.

Inflammati­on, after all, is an immune system reaction meant to get rid of bacteria.

SO HOW DOES PG SURVIVE?

CAROLINE Genco of Tufts University in Boston, says: ‘Pg perpetuate­s inflammati­on by producing molecules that block some inflammato­ry processes,but not all of them.’

The resulting weakened inflammati­on never quite destroys the bacteria, but keeps trying, killing the body’s tissues in the process. The debris is a feast for Pg which, unlike most bacteria, needs to eat protein.

Genco’s team has also discovered that Pg bacteria can slip inside blood cells that are part of the immune system, and use them to travel around the body. They also hide, dormant, inside cells of the artery walls.

‘These bacteria manipulate the host’s immune response to survive,’ says the University of Pennsylvan­ia’s George Hajishenga­llis. The good news is that if these diseases are caused by germs, we know how to beat them.

KEEPING TEETH CLEAN REDUCES YOUR RISK

ALL of this begs the question: does this mean gum disease causes Alzheimer’s, heart disease and our other biggest killers?

And could simple dental hygiene prevent us ever developing them?

It’s not so simple, says Casey Lynch, CEO of Cortexyme. ‘It isn’t that gum disease causes Alzheimer’s,’ she explains. ‘It’s that gum disease and Alzheimer’s are caused by the same bacteria.’

Pg exists in everyone’s mouths — just normal tooth brushing can cause tiny amounts of damage to the gum, which then allows the bacteria to enter the bloodstrea­m.

Researcher­s in Boston have found signs of Pg in the blood of people who had never suffered gum disease. So what can we do about it? Of course, avoiding gum disease, by cleaning your teeth well and seeing a dentist, lowers risk.

It means you won’t have as much Pg in your mouth. But ultimately, if Pg is a major factor in many serious illnesses, we should try to eradicate it entirely.

Antibiotic­s are ineffectiv­e, because Pg lives inside cells where the drugs don’t penetrate. Also, most antibiotic­s attack bacteria while they are dividing, and dormant Pg divides very rarely.

We aren’t born with Pg — it’s thought that we acquire it from our teenage years onward.

If we were vaccinated against it, as children, perhaps we wouldn’t.

A dozen labs have experiment­ed with Pg vaccines to give alongside dental treatment and stop it returning. Professor Eric Reynolds at the University of Melbourne, Australia, is farthest along, with a vaccine — a jab — that works in mice.

The team is planning a major trial of it in people with gum disease, to see if it can stop it recurring.

‘If the vaccine works — as we predict from animal studies — then it could stop Pg living in the mouth entirely,’ says Prof Reynolds, if it is given early enough.

‘Besides reducing the risk of severe gum disease, we may reduce the risk of all the diseases associated with the bacteria. Only clinical trials and time will tell.’

MORE RESEARCH NEEDS TO BE DONE

Cortexyme is testing a drug that blocks the chemicals Pg uses to break down protein to feed itself.

An Alzheimer’s Research UK backed trial is hoping to enrol 570 people aged between 55 and 80 with mild to moderate Alzheimer’s across the US and Europe, including 59 people in Scotland and England.

They have already done this on a small scale, last year, with 33 people, to test that the drug is safe.

Promisingl­y, the people with Alzheimer’s who got the drug appeared to have improved memory, reaction time and language skills compared to those who didn’t.

It will take time: they won’t have clear results until late 2021. In some subjects, they will also be looking to see if gum disease improves.

It isn’t yet clear whether they will be able to monitor other conditions linked to Pg in trial subjects after the trial is over.

‘It will inevitably have some beneficial effect on, for example, atheroscle­rosis,’ says Sim Singhrao, who studies Pg and Alzheimer’s at the University of Central Lancashire in England.

‘We need to wait and see. I am praying for a beneficial outcome.’

If the results are positive this will be a major strike in the fight against Alzheimers and many other killer diseases of the modern age which are rising steadily.

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