Alzheimer’s Disease: Human cells could be gene-edited to reduce risk

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Human brain cells could be gene-edited to reduce the risk of developing Alzheimer’s disease, scientists claim

  • Researchers are examining methods to alter genes within the human brain
  • This genetic variant could reduce the risk of developing Alzheimer’s disease
  • The variant is found naturally in one in 150 people living in Scandinavia
  •  Future techniques could see the variant switched on in eggs and sperm

Cells in the human brain could one day be edited by scientists to prevent the development of Alzheimer’s disease, a new study suggests.

The causes of Alzheimer’s are still not well understood, but a leading theory is that it is triggered by the build-up of a protein called beta-amyloid outside the brain cells. 

Researchers from Laval University in Canada have been investigating how a key gene in human nerve cells could reduce the formation of this protein.

Many variants of this gene increases beta-amyloid production, but one variant, called A673T, instead reduces it.

A673T was first discovered in 2012, and is only active in one in 150 people in Scandinavia, but those that have it are four times less likely to get Alzheimer’s. 

The researchers believe that switching on this gene variant in brain cells could reduce the production of beta-amyloid and thereby reduce Alzheimer’s risk.

One in four people over the age of 90 develop Alzheimer’s, a condition thought to be triggered by a build up of a protein called beta-amyloid outside the brain cells

As the A673T variant doesn’t become relevant until later in life, it isn’t selected for by evolution, according to the study authors. 

It differs from other variants of the gene by a single DNA letter.

Researchers showed that, by editing this one DNA letter, they were able to activate the A673T variant in brain cells growing in a culture dish. 

Jacques Tremblay and colleagues say this is the first step to proving that engineering the variant into brains could have the same benefits as inheriting it. 

The team are still refining the technique before they try it on animals.

The researchers initially used a CRISPR technique called base editing, which allows the direct, irreversible conversion of a DNA base into another, targeted base.

However, they have now switched to a relatively new method called prime editing – a ‘search and replace’ technique for editing genomes that directly writes new genetic information into a targeted DNA site using a fusion protein.  

Working with cells in a dish they managed to edit about 40 per cent of the cells, but they think a higher proportion might be needed for it to work in a human brain. 

They worked with a process known as base editing, a relatively new method that allows the direct, irreversible conversion of a DNA base into another, targeted base

They worked with a process known as base editing, a relatively new method that allows the direct, irreversible conversion of a DNA base into another, targeted base

They worked with a process known as base editing, a relatively new method that allows the direct, irreversible conversion of a DNA base into another, targeted base

This genetic variant was first discovered in 2012 in a few people of Scandinavian ancestry and is present in one in 150 people in Scandinavia - but rare elsewhere

This genetic variant was first discovered in 2012 in a few people of Scandinavian ancestry and is present in one in 150 people in Scandinavia - but rare elsewhere

This genetic variant was first discovered in 2012 in a few people of Scandinavian ancestry and is present in one in 150 people in Scandinavia – but rare elsewhere 

The team say another major issue is that, by the time people start to show symptoms of Alzheimer’s, it could be too late to edit the genes to make a difference.

However, this is true of any treatment for Alzheimer’s, according to Selina Wray from University College London, who was not involved in the research.

She said all possible treatments, including gene-editing’ should still be pursued by researchers, as eventually something will work. 

Tremblay said the change could be made in sperm, eggs or embryos in future, so people with a family history of Alzheimer’s are born with the A673T variant. 

The findings have been published on the preprint server bioRxiv.  

WHAT IS DEMENTIA? THE KILLER DISEASE THAT ROBS SUFFERERS OF THEIR MEMORIES

Dementia is an umbrella term used to describe a range of neurological disorders

Dementia is an umbrella term used to describe a range of neurological disorders

Dementia is an umbrella term used to describe a range of neurological disorders

A GLOBAL CONCERN 

Dementia is an umbrella term used to describe a range of progressive neurological disorders (those affecting the brain) which impact memory, thinking and behaviour. 

There are many different types of dementia, of which Alzheimer’s disease is the most common.

Some people may have a combination of types of dementia.

Regardless of which type is diagnosed, each person will experience their dementia in their own unique way.

Dementia is a global concern but it is most often seen in wealthier countries, where people are likely to live into very old age.

HOW MANY PEOPLE ARE AFFECTED?

The Alzheimer’s Society reports there are more than 850,000 people living with dementia in the UK today, of which more than 500,000 have Alzheimer’s.

It is estimated that the number of people living with dementia in the UK by 2025 will rise to over 1 million.

In the US, it’s estimated there are 5.5 million Alzheimer’s sufferers. A similar percentage rise is expected in the coming years.

As a person’s age increases, so does the risk of them developing dementia.

Rates of diagnosis are improving but many people with dementia are thought to still be undiagnosed.

IS THERE A CURE?

Currently there is no cure for dementia.

But new drugs can slow down its progression and the earlier it is spotted the more effective treatments are.

Source: Alzheimer’s Society 

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