Scientists say gene editing could eliminate Down syndrome

Cutting-edge gene editing technology could eradicate Down syndrome, according to Japanese scientists.

Down syndrome, which causes a range of developmental differences and affects 1 in 700 newborns in the United States, is caused by the presence of an extra copy of chromosome 21.

The extra chromosome, also known as trisomy 21, causes cellular overactivity, compromises a range of processes within the body, and can manifest in distinctive physical traits, learning difficulties, and health concerns.

Now new research out of Mie University in Japan suggests that by using the DNA-modifying tech CRISPR, it is possible to remove the surplus chromosome in affected cells and bring cellular behavior closer to typical function.

CRISPR-Cas9 is a gene-editing system that utilizes an enzyme to identify specific DNA sequences. Once the enzyme locates a matching site, it snips through the DNA strands.

Ryotaro Hashizume and his colleagues designed CRISPR guides to target only the trisomy 21 chromosome, a process called allele-specific editing, which directs the cutting enzyme to the desired spot.

When they used it on lab-grown cells, removing the extra copy of the gene normalized the way the genes expressed themselves in the body — suggesting that the genetic burden had been removed.

They also found that after the extra chromosome was removed, genes tied to nervous system development were more active and those related to metabolism were less active. This backs up previous research that found extra copies of chromosome 21 disrupt brain development during early fetal growth.

Researchers also tested their CRISPR guides on skin fibroblasts, which are mature, non-stem cells taken from people with Down syndrome.

In these fully developed cells, the editing method successfully removed the extra chromosome in a number of cases.

After removal, these corrected cells grew faster and had a shorter doubling time than untreated cells, suggesting that removing the extra chromosome may help with the biological strain that slows down cell growth.

But the CRISPR can affect healthy chromosomes, too, and researchers are refining their program so that it only attaches to the extra copy of chromosome 21.

This work proves that, rather than making small fixes, CRISPR can eliminate an entire chromosome.

The scientists published their findings in PNAS Nexus.

Hashizume and his team are hopeful that their work may be used to design regenerative therapies and treatments that address genetic surplus at its source.

Researchers will continue to analyze the risks of DNA changes and monitor how modified cells function over time and their viability in real-world settings.

A recent case study explored a medical mystery related to Down syndrome; the brain of an American woman with Down syndrome showed all the classic signs of Alzheimer’s disease, yet she remained symptom-free throughout her lifetime.

People with Down syndrome face a much higher risk of developing Alzheimer’s-related dementia as they age — an estimated three to five times higher than the general population.

Scientists are still working to pinpoint the exact cause, but it’s believed that the extra copy of chromosome 21 drives the overproduction of amyloid precursor protein. This excess production leads to the buildup of amyloid beta plaques in the brain, a hallmark of Alzheimer’s disease.