Breakthrough new treatment could REVERSE Down syndrome

Cutting-edge technology could one day transform treatment for Down syndrome, as researchers have successfully deleted an extra chromosome in lab-grown cells.

Down syndrome – which occurs when a person has three copies of chromosome 21 instead of two – alters brain development and can cause intellectual disability, learning difficulties and other health challenges. 

It affects about one in 700 births in the US, with an estimated 250,000 people living with the condition.

Scientists from Mie University in Japan have used CRISPR-Cas9, a DNA-editing tool often described as ‘molecular scissors,’ to cut away the surplus chromosome in cells.

Their system was able to distinguish the duplicated chromosome from the two original parental copies, ensuring the cell kept one from each parent rather than two identical versions. 

Those corrected cells began showing more typical patterns of gene activity and cellular behavior, especially in pathways linked to brain development.

While the results are a striking proof of concept, experts stress that this research is still far from becoming a therapy.

‘Removing an extra chromosome from a single cell has been possible for more than a decade, and CRISPR has made the process more precise,’ Dr Roger Reeves of Johns Hopkins University School of Medicine told the Daily Mail.

‘But a human body contains trillions of cells, each carrying the extra chromosome, so there is currently no realistic way to apply this as a treatment. Lab-grown cells are powerful research tools, but they don’t replicate the full complexity of a developing human.’ 

Scientists have long struggled to pinpoint exactly which genes on chromosome 21 are responsible for the traits and health problems seen in Down syndrome. 

One major challenge is that people’s genetic backgrounds vary, making it harder to find consistent patterns across individuals. 

This makes it difficult to identify clear genetic ‘signatures’ that can be directly targeted for therapy.

While there is no cure or treatment for the disorder, the Japanese scientists believe their method could pave the way for intervention. 

The technique was tested in two types of lab-grown cells: induced pluripotent stem cells reprogrammed from adult tissue, and skin fibroblasts. 

CRISPR-Cas9 was employed to cut at multiple sites on the extra chromosome 21. 

By creating breaks in several places at once, the cell was forced to eliminate the damaged chromosome entirely. 

Because each cell with Down syndrome has three copies of chromosome 21, the scientists designed the system to distinguish between the duplicated copy and the two original parental copies, making sure the wrong one was not removed. 

To boost the odds of success, the team also suppressed the cell’s DNA repair system. 

Normally, cells quickly try to patch up broken DNA. But in this case, shutting down that repair ability made it more likely the whole extra chromosome would be lost instead of fixed. 

After editing, only a small fraction of the millions of cells tested lost the extra chromosome. 

Reeves said that the scale of the challenge is immense. 

‘Theoretically, more than 800 million cells would need to have the extra chromosome 21 removed to create a “typical” person,’ he said.

‘Right now there is no way to target every cell, and most would die in the process. That makes this approach impossible to apply to a living baby.’

Most Down syndrome research focuses on managing symptoms or treating associated health conditions rather than correcting the genetic cause.

For example, fetal surgery can sometimes repair heart defects before birth, and postnatal therapies often target learning difficulties or other medical complications. 

By contrast, directly removing the extra chromosome tackles the root of the disorder, but comes with technical and ethical challenges that make it far more complex.

The Japanese team acknowledges the limitations, noting that delivering CRISPR edits to the right cells in the body, avoiding harmful off-target DNA damage and ensuring safety in embryos or living people are major hurdles still to be solved.

Even if science advances, there are ethical barriers to using gene-editing tools like CRISPR on human embryos.

The method is controversial and currently banned in most countries, in part due to concerns about unintended consequences and the potential for ‘designer babies’.

Even so, researchers said the work is an important milestone, showing that CRISPR can cleanly eliminate a whole chromosome, which opens new doors for studying Down syndrome at the cellular level and may one day guide future therapies.