Review: Understanding Rare Genetic Diseases in Low Resource Regions Like Jammu and Kashmir – India
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.
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. Mongkolchon – stock.Adobe.ComCRISPR-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.
Hashizume and his team 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. Gorodenkoff – stock.Adobe.ComAfter 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.
Researchers also tested their CRISPR guides on skin fibroblasts, mature, non-stem cells taken from people with Down syndrome. Yakobchuk Olena – stock.Adobe.ComPeople with Down syndrome often deal with a range of health concerns, including developmental delays and intellectual disabilities.
Roughly half of people with Down syndrome are born with a congenital heart defect — most commonly atrioventricular septal defect, a hole in the center of the heart.
They're also more likely to have problems with digestion, immunity, weight, sleep apnea, seizures, hearing, vision and teeth. They're at higher risk for leukemia and spinal problems, as well as thyroid conditions.
Additionally, they 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.
Yet eliminating Down syndrome has proven to be a controversial topic. Iceland has made headlines over the years for nearly eradicating it in its population of just under 400,000, largely because nearly all women there choose to abort when their prenatal screening tests are positive for it.
"When we start listening to what people with Down syndrome themselves have to say about this … they find it disturbing … and we hear the same stories from their families," Ástríður Stefánsdóttir, a medical doctor and a professor in applied ethics at the University of Iceland, told ABC News Australia.
Ethical Concerns Rise After Scientists Use Gene Editing To Erase Down Syndrome-Causing Chromosome
Scientists in Japan have used gene-editing technology to remove the extra chromosome responsible for Down syndrome, at least in lab-grown human cells.
The project, led by Dr. Ryotaro Hashizume of Mie University, used CRISPR-Cas9 to target the trisomy 21 chromosome, the root cause of Down syndrome, which affects 1 in every 700 births.
Removing the extra chromosome altered cell behavior dramaticallyImage credits: Ermolaev Alexandr/Adobe Stock (Not the actual photo)
Down syndrome occurs when a person is born with three copies of chromosome 21 instead of two.
That surplus genetic material causes developmental differences and raises the risk for a number of health issues, including heart defects, immune dysfunction, thyroid disease, and Alzheimer's-related dementia.
To address this, Dr. Hashizume and his team designed special CRISPR guides that zeroed in on the extra chromosome, and only that one.
Image credits: Nexa/Adobe Stock
In both stem cells and mature skin cells taken from people with Down syndrome, the gene-editing tool successfully removed the extra chromosome without affecting the healthy ones.
Once the surplus was gone, the cells began to behave differently, according to a Sci Tech Daily report.
Genes tied to brain development also became more active. Genes that were previously overactive, such as those linked to inflammation or metabolism, quieted down as well.
Image credits: thebiomics
The edited cells even grew faster and divided more normally, suggesting that the excess chromosome had placed some biological strain on them.
This is the first time CRISPR has been used to erase an entire chromosomeDr. Hashizume and his team's study marked the first time scientists have successfully used CRISPR to delete a full chromosome from human cells.
The team accomplished this through a process called allele-specific editing, which essentially involves training CRISPR to find only the rogue copy of chromosome 21.
To improve their odds, researchers temporarily suppressed the cells' natural DNA repair mechanisms. The strategy paid off, and it made the deletions more consistent.
The team's method worked in differentiated, non-dividing cells, too, not just in embryonic stem cells.
This hinted at the method's possible therapeutic potential in older patients.
It's not ready for real-world treatment, but the implications are hugeImage credits: CNBC International
Researchers are quick to stress that this discovery is still years away from being used in humans, since the method could affect good chromosomes, too.
Still, the study proves something once thought impossible: that a whole chromosome can be removed in a precise manner.
Dr. Hashizume and his team stated that the next steps will involve refining their method to prevent unintended edits and testing its effects over time.
Image credits: CNBC International
If successful, the approach could pave the way for regenerative therapies that begin at the genetic root of Down syndrome.
Some netizens were wary of the scientists' method.
"I hope (the) solution is not coming with another problem," one commenter wrote.
Image credits: McGovern Institute
"The road to h*ll is paved with good intentions," another wrote.
"Playing with nature is scary," another commenter stated.
Others, however, were excited about the potential of the scientists' study.
"I love people with Down Syndrome, and this would be a wonderful blessing!" wrote one commenter.
"This will be amazing. Many, and in some countries, most fetuses with Down syndrome are aborted. This will be a great breakthrough," another wrote.
The ethics of "erasing" Down syndrome still raise serious questionsWhile the science is promising, the idea of eliminating Down syndrome has sparked deep ethical debate, according to the New York Post.
Critics worry that such technologies could devalue the lives of people with the condition.
Image credits: DC Studio/Adobe Stock (Not the actual photo)
Iceland, for example, has practically eradicated the condition, but this was because almost all expectant mothers terminate pregnancies after a positive prenatal Down syndrome screening.
Such practices have drawn both support and criticism.
Image credits: Nexa/Adobe Stock (Not the actual photo)
Ástríður Stefánsdóttir, a medical doctor and a professor in applied ethics at the University of Iceland, described these concerns.
"When we start listening to what people with Down syndrome themselves have to say about this … they find it disturbing … and we hear the same stories from their families," he said.
Netizens largely welcomed the developments of Dr. Hashizume and his team's researchWhat Is Mosaic Down Syndrome? Parents Open Up - TODAY
Emma McLean is a 6-year-old girl who loves Taylor Swift, reading books, playing the drums and hanging with her little sister. While Emma has Down syndrome — specifically a rare type called Mosaic Down syndrome — some people don't believe it.
"At the hospital, doctors and nurses kept saying, 'She doesn't look like she has Down syndrome,'" Melissa McLean, 39, who is Emma's mother, tells TODAY.Com. "I've heard other comments like, 'Are you sure she has it?'"
Yes, McLean is sure — 15 weeks into her pregnancy, McLean had a blood test to determine whether her baby had any genetic abnormalities. McLean and her husband learned there was a 90% chance their daughter would have Down syndrome, a diagnosis she says they embraced with a "Whatever happens, happens" attitude.
Emma was diagnosed with Down syndrome 24 hours after she was born, however the McLeans had never heard of Mosaic Down syndrome, until doctors confirmed it when Emma was 2 months old.
What is Mosaic Down syndrome?Down Syndrome is a genetic condition in which a person is born with an extra copy of chromosome 21, according to the Cleveland Clinic. Whereas people are usually born with 46 chromosomes, those with Down Syndrome have 47.
There are three types of Down syndrome.
Although Down syndrome is a genetic condition, it can also occur randomly when the fetus develops. Experts aren't exactly sure why it happens but one risk factor is age: People who give birth over 35 are more likely to have a baby with Down syndrome, according to Cleveland Clinic.
People with Down syndrome can share physical characteristics like flatter faces, slanted and upward eyes, a shorter neck and smaller extremities. Also common are developmental delays with walking or talking, cognitive impairment in the areas of social-emotional skills or behavioral issues.
Not everyone with Down syndrome — including those with Mosaic Down syndrome — looks and acts the same.
"The phenotype — which is the 'look' of Down syndrome — could vary," Dr. Mary Wong, a physician at Cleveland Clinic's Children's Center for Down Syndrome, tells TODAY.Com. "It's very possible that an individual with Mosaic Down syndrome's phenotypic features could be less pronounced."
Wongs adds, "For example, I have a patient with Mosaic who is one of triplets. Out of the three kids, (my patient) is the tallest and heaviest, even though Down syndrome kids are usually the shortest, compared to the general population."
People with Mosaic Down syndrome can share the cognitive and physical challenges as those with Trisomy 21 and Translocation Down syndrome. "There's a wide range of abilities," says Wong.
Emma didn't walk until she was 2-and-a-half and she was minimally verbal until last year, says her mom. While Emma is in a typical school and a general classroom, "She is a little behind her peers developmentally and with her receptive understanding, but she's doing well so far," says McLean, adding that her daughter participates in inclusive cheerleading and baseball programs.
McLean says people have inferred things about her daughter.
"Some people believe that people with Mosaic Down syndrome don't have as many struggles, but that's a slippery slope and would be very hard to generalize," says McLean. An acquaintance once told McLean that Emma has "the best kind of Down syndrome" out there.
"I know people are trying to make you feel better, but it's not necessary," says McLean. "Unless you're the parent of a child with a disability, you might not understand that what you're saying is more damaging than, 'Thanks for educating me.'"
'I grew up thinking I was a typical kid'When 25-year-old Ashley Zambelli learned she had Mosaic Down syndrome in 2023, her parents were "shocked" — despite Zambelli having conceived three children with Trisomy 21.
"My dad laughed and said, 'No way!'" Zambelli, a stay-at-home mom of four, tells TODAY.Com.
It was also news to Zambelli, as Down syndrome is often diagnosed during pregnancy or shortly after birth.
Reflecting on her childhood in a TikTok video, Zambelli noted early indicators of her diagnosis: She had low muscle tone in particular areas of her body, loose ligaments and a habit of sitting in a "W" shape, when a person sits on their bottom with their knees in front and their legs splayed behind them.
According to Wong, people with Down syndrome may sit in a "W" position due to hypotonia (low muscle tone), and it's an easier way to prop up their bodies.
Zambelli says she did struggle academically in high school and later dropped out of college, though, "My cognitive impairment was not obvious or strong enough for someone to see and diagnosis it ... I grew up thinking I was a typical kid."
She suspects her condition went unnoticed largely because, "I don't have any of the phenotypes associated with Down syndrome," she says. "I always knew something was different with me as a child because of the medical stuff — my parents took me to doctors ... And the best doctors could come up with was maybe I had lupus ... Without having the phenotype, doctors hadn't even thought to order genetic testing."
Zambelli later conceived three children with Trisomy 21: Her daughters Lillian, 4, and Katherine, 1, and a baby boy she miscarried in 2019. Zambelli's other two children, Evelyn, 3 and Damian, 11 months, do not have Down Syndrome.
While pregnant with Katherine (who tested positive for Down syndrome in utero), Zambelli's OB/GYN encouraged her to undergo genetic testing herself. "She hadn't ever had a patient with three confirmed cases of Down syndrome during pregnancy," she says.
Zambelli's blood tests were negative for Down syndrome and other genetic abnormalities — but a buccal smear test of her cheek revealed Mosaic Down syndrome in 3% of her cells, which does not reflect the totality of mosaicism in her body.
"I do not have any Trisomy 21 in my blood cells, only in my tissue cells," says Zambelli.
Wong explains: "If the blood test (karyotype) is negative and there is a strong clinical suspicion ... Then genetics will do additional testing."
According to Zambelli, she doesn't have any cognitive issues that "meet medical standards" but she struggles with reading comprehension and problems with her joints, ligaments and heart, like others with Down syndrome.
Parenting with Mosaic Down syndromeZambelli says having Mosaic Down syndrome makes her a more sensitive parent to her two diagnosed children.
"I know how to help and guide my kids, especially my 4-year-old, who is getting older and interacting with other kids," she says.
Zamebelli says she has wavering emotions about her adult diagnosis.
"I'm glad I was diagnosed later in life because I was able to grow up without any stigmatizing, but sometimes I wish it was diagnosed early ... Because I may have done better in school if I had more resources," she says. "Medically, I may have been in a better spot than I am today."
As for parenting a daughter with Mosaic Down syndrome, McLean loves her in all her individuality.
"We were told that Emma would probably never walk or talk and that does happen for some people — but it's not everyone," she says. "There are so many beautiful parts of life that we can experience now because of Emma."
McLean adds, "If we didn't have a child with a disability, we would be different people ... Emma has changed everybody."
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