Down Syndrome Treatment Study Shows Experimental Drug Reverses Cognitive Deficits In Mice

 by David Freeman from the Huffington Post:
There's still no cure for Down syndrome, but recent research is raising hopes that drugs can be found to counter the cognitive deficit that characterizes the genetic disorder.
In July, University of Massachusetts researchers said they had found a way to shut down the extra chromosome that causes the syndrome, at least in test tubes. And now comes word that scientists have identified a compound that brings dramatic improvements in learning and memory in mice bred to have a Down-like condition. One injection of the compound given on the day of birth seemed to work by allowing the animals' cerebellums to grow to full size.
"Most people with Down syndrome have a cerebellum that's about 60 percent of the normal size," Dr. Roger H. Reeves, a professor at Johns Hopkins University and one of the scientists behind the research, said in a written statement. "We treated the Down syndrome-like mice with a compound we thought might normalize the cerebellum's growth, and it worked beautifully... We were able to completely normalize growth of the cerebellum through adulthood with that single injection."

Could it be a 'cure'? Breakthrough prompts Down syndrome soul-searching

from JoNel Aleccia from NBC News Blog:
In the 14 years since her daughter, Rachel, was born with Down syndrome, Jawanda Mast has always been clear that she’d change the condition if she could.
“I couldn’t love her more, but I would give almost anything to take away that extra chromosome,” the Olathe, Kansas, mom wrote on her blog. “While I may know she’s perfect, the world doesn’t.”
But when Massachusetts scientists announced recently that they’ve found a way to silence the chromosome that causes trisomy 21, also known as Down syndrome, it rocked Mast – and the rest of the disability community.
“It’s so hard to imagine you could actually do that,” Mast told NBC News. “Yes, I would take away the challenges, I would take away the health risks. But now I also stop and say, ‘Oh my goodness, how would that impact the rest of her?’”

Brain Cells Grown from Skin Cells Reveal Certain Effects of Down Syndrome

from Counsel & Heal by Cheri Cheng:
Brain disorders, such as Down syndrome, which is the most common type of hereditary intellectual disability, are some of the hardest conditions to understand. There are multiple mechanisms and levels of activity that occur in the brain that make it difficult to pinpoint the exact relationships between genetic mutations and the symptoms they cause. In Down syndrome people, in particular, researchers know that the condition results from an extra copy of a single chromosome. Researchers do not know how this one copy could result in a wide range of symptoms. In an attempt to understand this, researcher Anita Bhattacharyya, a neuroscientist at the Waisman Center at the University of Wisconsin-Madison, studied brain cells that were created from the skin cells of people with Down syndrome.
"Even though Down syndrome is very common, it's surprising how little we know about what goes wrong in the brain. These new cells provide a way to look at early brain development," she explained.

Molecular Roots of Down Syndrome Unraveled

Neurons from a typical mouse (left) are longer and fuller than neurons from a mouse lacking SNX27 (right). (Credit: Image courtesy of Sanford-Burnham Medical Research Institute)

from Science Daily:
Researchers have discovered that the extra chromosome inherited in Down syndrome impairs learning and memory because it leads to low levels of SNX27 protein in the brain.
What is it about the extra chromosome inherited in Down syndrome -- chromosome 21 -- that alters brain and body development? Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have new evidence that points to a protein called sorting nexin 27, or SNX27. SNX27 production is inhibited by a molecule encoded on chromosome 21. The study, published March 24 in Nature Medicine, shows that SNX27 is reduced in human Down syndrome brains. The extra copy of chromosome 21 means a person with Down syndrome produces less SNX27 protein, which in turn disrupts brain function. What's more, the researchers showed that restoring SNX27 in Down syndrome mice improves cognitive function and behavior.
"In the brain, SNX27 keeps certain receptors on the cell surface -- receptors that are necessary for neurons to fire properly," said Huaxi Xu, Ph.D., professor in Sanford-Burnham's Del E. Webb Neuroscience, Aging and Stem Cell Research Center and senior author of the study. "So, in Down syndrome, we believe lack of SNX27 is at least partly to blame for developmental and cognitive defects."

SNX27's role in brain function
Xu and colleagues started out working with mice that lack one copy of the snx27 gene. They noticed that the mice were mostly normal, but showed some significant defects in learning and memory. So the team dug deeper to determine why SNX27 would have that effect. They found that SNX27 helps keep glutamate receptors on the cell surface in neurons. Neurons need glutamate receptors in order to function correctly. With less SNX27, these mice had fewer active glutamate receptors and thus impaired learning and memory.

Illumina Buys Maker of Test for Down Syndrome

from Deal Book by Andrew Pollack:
Illumina, the leading manufacturer of DNA sequencing machines, said on Monday that it would buy the privately held Verinata Health for at least $350 million in cash to expand its push into the diagnostics business.
Verinata, based in Redwood City, Calif., sells a test that uses a blood sample from a pregnant woman to determine whether her baby will have Down syndrome or some other chromosomal abnormalities.
Such tests, which have been available for only about a year, have been rapidly catching on as an alternative, in some situations, to invasive tests like amniocentesis that carry a slight risk of inducing a miscarriage.
Illumina’s stock fell almost 8 percent in early trading on Monday, though that was probably more because of reports that Illumina itself would not be acquired by Roche Holding, the Swiss pharmaceutical and diagnostics company. Illumina shares closed at $50.88, down 7 percent.
Roche’s chairman, Franz B. Humer, was quoted on Sunday by a Swiss newspaper, Sonntags Zeitung, as saying a deal was off because Illumina wanted too high a price.
In April, Roche had dropped a hostile bid for Illumina, valued at $51 a share, or about $6.7 billion.
But a different Swiss newspaper had reported in December that Roche was trying to buy Illumina again, this time for $66 a share. Neither Illumina nor Roche commented publicly on that report.
Both Roche’s interest in Illumina and Illumina’s acquisition of Verinata suggest that DNA sequencing, which until now has mainly been used for research studies like the Human Genome Project, is moving toward being used for medical diagnosis.
Illumina wants to be more than a seller of sequencing machines. It already offers a service sequencing the genomes of people to help diagnose rare diseases or figure out the best treatment for a cancer. In September, it bought BlueGnome, a British company that uses sequencing to screen for various genetic abnormalities.
“The agreement with Verinata demonstrates Illumina’s commitment to developing innovative diagnostic solutions and providing our partners with the most advanced technologies for improved patient care,” Jay T. Flatley, chief executive of Illumina, said in a statement.
Verinata’s test, called Verifi, uses sequencing to analyze fragments of fetal DNA that can be found in a pregnant women’s blood. That allows for detection of Down syndrome, in which a person has three copies of chromosome 21 instead of the usual two.
Such noninvasive tests for Down syndrome appear to be catching on rapidly. Verinata, however, is believed to substantially lag the market leader, Sequenom, in market share.
Sequenom, a publicly traded company, introduced the first noninvasive Down syndrome test in October 2011.
It said on Sunday that it had performed 60,000 of its MaterniT21 Plus tests in 2012, and by the end of the year was operating at an annualized run rate of 120,000 tests.
Others selling or developing such tests include Ariosa Diagnostics and Natera. The companies are involved in various patent lawsuits against one another. They are also broadening their tests to detect chromosomal abnormalities beyond Down syndrome, including those linked to abnormalities in the sex chromosomes.
Some of these other companies use Illumina sequencers to perform their tests. It is possible they may now become more reluctant to rely on machines made by a company that is a competitor.
Illumina said there were about 500,000 high-risk pregnancies a year in the United States that would be candidates for a noninvasive prenatal test. It said the potential market for such tests would be more than $600 million in 2013.
Verinata said on its Web site that it would continue to operate as a subsidiary of Illumina. Beyond the initial payment of $350 million, Verinata shareholders will be eligible to receive up to an additional $100 million in milestone payments through 2015.
Illumina said the deal would dilute its earnings per share by 20 cents in 2013 but add to them in 2014.
Bank of America Merrill Lynch and Covington & Burling advised Illumina on the deal.
Illumina made its announcement on the eve of the J. P. Morgan Healthcare Conference in San Francisco, an annual Wall Street and medical industry gathering at which numerous companies make announcements.

Living with Down Syndrome

By Christina Kristofic from Philly Burbs.com:
If you ask Kathryn Drenth to tell you about her Down syndrome, she’ll probably pull down her shirt and show you the scar from the open heart surgery she had when she was 6 months old. Her mother immediately will make her cover up and say, “Remember what we said about privacy.”Mariah Drenth-Cormick is trying to stop that demonstration now because she knows it won’t be long before that’s a social taboo.“I don’t think she thinks Down syndrome is any different from the scar on her chest,” Mariah told a class at Delaware Valley College recently.
Seven-year old Kathryn thinks she’s just like other kids her age.
And in some ways, she’s right.
Kathryn has the same energy and excitement for life that other kids her age do. She loves going to Simon Butler Elementary School, where she sits in a mainstream class and studies the same things other second-graders do.
Kathryn loves playing with her classmates at recess or after school. She loves spending time at home with her family, where she might watch cartoons, play games, lead a dance party, read to her baby dolls or fight with her younger brother.
But Kathryn and her classmates are only 7. And Kathryn’s classmates don’t have an extra chromosome that will slow their physical and mental development.
So how much longer will Kathryn be like most of the other kids? When will they outpace her?
Mariah Drenth-Cormick, one of the co-chairwomen of the Bucks County Down Syndrome Interest Group, knows her daughter will always be behind other kids.
But she doesn’t know by how much.
Mariah said the geneticist at The Children’s Hospital of Philadelphia who officially identified Kathryn’s condition a few days after she was born told her that Kathryn would not be able to do basic problem-solving tasks. The example the geneticist gave Mariah, which she gave the students at DelVal was: If someone told Kathryn to take the elevator to the third floor of a building and use it again to get back to the first floor, and a fire broke out somewhere in the building, Kathryn would not know to take the stairs and would insist on waiting for the elevator to get out. But Mariah knows that’s not true of her daughter.
“This girl can connive anything out of anyone and she has very good negotiating skills,” Mariah said.
Mariah is letting Kathryn show her — and others — what Down syndrome is.
As one of the co-chairs of the Bucks County Down Syndrome Interest Group, Mariah represents about 160 families of children with Down syndrome in Bucks County. She regularly takes Kathryn to meet women who are pregnant with or just gave birth to babies with Down syndrome, so the women can “see what a kid with Down syndrome looks like, what they can do and can’t do, how they bend in half.”
The visit to DelVal was the first time Mariah took Kathryn to speak to a college class.
“I just want to create the normalcy about it,” she said.
“Yes, it’s an extra chromosome. It’s not that scary. I think when people hear Down syndrome, especially older people, they have a preconceived notion that you put the child in an institution. We have special education, an IU, so many wonderful supports in place... Kathryn is only one grade-level behind. She can do everything on the playground except for the really high monkey bars. I can’t do the really high monkey bars. She’s just had such an awesome team and support that has helped her succeed.”
Kathryn crawled at 10 months and walked at 2 years old — later than most kids.
She started occupational therapy, physical therapy and speech therapy as a toddler, so she is more advanced than some other kids her age who have Down syndrome. Mariah said she knows other children in the area who have Down syndrome who have to go to another school that offers more support for them.
Kathryn’s condition means she has trouble reading and writing some words her mainstream classmates already have mastered. Her speech isn’t as clear as theirs. And because she has low muscle tone and control, her handwriting is bigger and sloppier.
So she gets extra help each day from therapists and learning support teachers.
The other kids in her mainstream class, who might know that Kathryn is different, don’t treat her like she is.
“This group of second-graders is one of the kindest groups I have ever met. There is this genuine respect the kids have for each other,” said Susan Zubak, Kathryn’s second-grade teacher. “And Kathryn is a bit of a celebrity at times in here. Kids will actually go out of their way to have the opportunity to read with Kathryn.”
Being part of a mainstream class is good for Kathryn’s growth and development, Zubak said, because it gives Kathryn the opportunity “to come in and see some higher-level thinking skills going on and model herself off what she sees going on in the classroom.”
The kids in the mainstream class learn from it, too. Rebekah Detweiler, Kathryn’s learning support teacher said, they can get to know Kathryn “and see that everyone’s different and there’s all different kinds of people.”
And then, Detweiler said, Kathryn and other children with development disabilities can “feel like they’re included with their community of learners.”
Kathryn’s family tries to treat her like a typical child her age and sets high standards for her. Mariah said, “She has boundaries. ‘Here’s what we expect of you in public. Don’t lift your skirt. Sit like a lady.’ “
Some of the other rules: Say “please” and “thank you,” don’t give other people attitude.
Kathryn follows the rules most of the time — as well as any 7-year old can. And her parents remind her of the rules regularly.
“We want her to be an independent person who eventually has a job,” Mariah said. “If we coddle her and do things for her, she’s never going to learn to do things for herself.”
Mariah said she and her family want to see Kathryn have her own home one day and “have any opportunity a typical person would.”
“If she wants to go to college, we’ll find a college that will meet her needs,” Mariah said. “I think she can be anything she wants to be.”
If you ask Kathryn what she wants to be when she grows up, she’ll give you a different answer each time. She told a reporter one day that she wanted to be a teacher. She told the DelVal class she wanted to be a princess.
She has typical 7-year old dreams.

Christina Kristofic: 215-345-3079;
email, ckristofic@phillyburbs.com;
Twitter, @CKristofic

siblings Josh and Grace share a message about love and respect

Josh and Grace Curley created a slide show about love between siblings and respect for all people that has gone viral. Over a million people have viewed, liked, & shared the slide show on Facebook and imgur. This is a great example of the power of advocacy through something as simple as 18 pictures with words printed on notecards. Thank you Josh and Grace!

Text from the notecards on the slides:

• My names Josh and I'm 18 years old!
• This is my best friend and big sister Grace.
• Some say I have a disability...
• Grace says I have a ability that may be jealous of...
• the ability to love unconditionally, be non judgemental,
• and I'm not afraid to be me :-)
• I have Down syndrome
• I have a extra chromosome.
• Grace says "Real friends down count chromosomes"
• People sometimes use really mean words but ALOT of people love me
• These mean words Hurt but don't describe me at all
• I am... Silly
• Funny
• Loving
• Helpful
• Smart
• And I have feelings just like you and your friends
• I'll give you a chance, if you give me one too.

The Three Types of Down Syndrome

from Home Remedies for you .com:
Human chromosomes have a unique genetic code, which instruct and control the division, function as well as the growth of cells. Under normal circumstances, your cells contain 23 pairs of chromosomes, where one chromosome comes from your dad and the other from your mom. However, at times the cells could have three copies of a particular chromosome, instead of two. People who have three copies of the Chromosome 21 are born with Down syndrome. Other genetic problems occur when the duplicated chromosomes are other than Chromosome 21. Therefore Down syndrome is also commonly known as Trisomy 21.
Not a lot of people are aware of the fact that Down syndrome can be classified into three different kinds. Given below are facts about the three types of Down syndrome –

Standard Trisomy 21 or Nondisjunction Down syndrome
Around 90% to 95% of all the people who have Down syndrome are suffering from Standard Trisomy 21. Individuals who have 3 copies of Chromosome 21 in all the cells are born with this form of Down syndrome. Trisomy 21 occurs when there is an abnormal division of cells during the development of the egg cell or even the sperm cell. Around 88% of all Down syndrome instances come from the nondisjunction in the maternal gamete; while the paternal side constitutes of 8% of the total cases.

Mosaicism
Standard Trisomy 21 occurs when there is a nondisjunction in the gametes before conception, which affects all the cells present in the child’s body. However, at times only certain cells are affected by the abnormal division, while others are just fine. This is known as Mosaic Down syndrome, or Mosaicism. There are two ways in which this form of Down syndrome can occur. The first is a nondisjunction process that occurs during the earlier stages when the cell divides in the embryo that is normal, which results in few of cells being affected by Trisomy 21. The other way occurs when an embryo with Down syndrome goes through nondisjunction, but certain cells within the embryo return to the standard chromosome arrangement. This form of the disorder is quite rare and constitutes for about 1% or 2% of observed Down syndrome instances.

Translocation
Sometimes, Down syndrome is caused when part of Chromosome 21 becomes attached or trans-located to a different chromosome, before or during conception. People who have Translocation Down syndrome have the normal two copies of chromosome 21. However, they also have extra material from chromosome 21 attached onto the trans-located chromosome. Translocation Down syndrome is the only type that can be passed on from a parent to the child. This form of the disorder is also quite uncommon and constitutes for about 2% or 3% of observed Down syndrome instances.

References

• http://www.mayoclinic.com/health/down-syndrome/DS00182/DSECTION=causes
• Facts about Down syndrome. National Institute of Child Health and Human Development. http://www.nichd.nih.gov/publications/pubs/downsyndrome.cfm. Accessed Feb. 14, 2011
• Genetic conditions: Down syndrome. Genetics Home Reference. http://ghr.nlm.nih.gov/condition=downsyndrome. Accessed Feb. 14, 2011
• Birth defects: Down syndrome. Centers for Disease Control and Prevention. http://www.cdc.gov/ncbddd/birthdefects/DownSyndrome.htm. Accessed Feb. 15, 2011

Professor Lejeune – a patron saint of Down’s syndrome?

by Francis Phillips from the Catholic Herald:

The French geneticist’s Cause is needed more than ever

Another good news item from Rome Reports: at the current Rimini Conference of 2012 to discuss the economic crisis, education and inter-religious dialogue there is an exhibition to highlight the life and work of the late Professor Jerome Lejeune, 1926-1994, entitled “What is man that one is mindful of him?” It includes his writing desk, his microscope, his diaries and many photos. Professor Lejeune became world-famous in 1959 when, as a young Catholic doctor and scientist working in the field of genetics, he discovered the extra chromosome that causes Down’s syndrome or Trisomy 21, a common form of mental disability. His discovery opened up a whole new field of research and he was made the first professor of Fundamental Genetics at the Faculty of Medicine in Paris.
However, for Lejeune research was never an end in itself, though it brought him international recognition and, in 1969, the William Allen Memorial Award, the highest academic honour in genetics. According to Wiki, he was now “driven by a single ambition: to find a treatment that would bring relief to his patients as quickly as possible.” He viewed research “as inseparable from treatment and he was horrified as he gradually realised the consequences that misuse of his discovery would have for babies with Trisomy 21”, i.e. that it would be widely used to diagnose and then abort these disabled babies in the womb.
He wrote at the time, “That this rejection of medicine – of the whole biological brotherhood that binds the human family – should be the only practical application of our knowledge of Trisomy 21 is beyond heartbreaking.” According to his daughter Clara, who was to write her father’s biography, “Life is a Blessing” after his death from lung cancer on Easter Sunday 1994, he knew each of the 5000 patients in his clinic by their first name. His daughter said he decided he couldn’t accept abortion “not because he was a Christian but because he knew as a geneticist that life starts at conception.”
Lejeune became friends with another pro-life champion, the late Pope John Paul II who named him as the first president of the new Pontifical Academy for Life. He once told his daughter, without any bitterness, that his championship of life alongside academic research was to cost him the Nobel Prize. It also made him an outcast within the scientific community and his funding was withdrawn. He was not deterred. His daughter remembered that her father once came home to lunch and told the family about a little boy with Down’s syndrome who had seen a programme about pre-natal testing and who had begged him to save him from “those who want to kill us.” Clara Lejeune relates, “He was white and he said, “If I don’t protect them, I am nothing.” Professor Lejeune’s cause for sainthood is now being investigated.
Personally I hope his cause proceeds quickly. Never have we so needed the voices of doctors to defend life, whether those of disabled preborn babies, or now the elderly and sick. Lejeune knew that his mission as a doctor and geneticist was to save lives, not destroy them. When I read his biography I was deeply moved by its portrait of this humble man: a loving husband and father as well as a distinguished doctor. It actually inspired me (never having walked any distance in my life) to undertake a sponsored 25-mile walk in the millennium year 2000 for pro-life societies at university, which were then under attack from other “pro-choice” student groups. Never having done any fund-raising before, I managed to raise over £2000.
On a more personal note, when our youngest daughter was born with Down’s syndrome in 1990, I wrote for advice to Professor Lejeune at his research centre in Paris. He replied in longhand by return of post. I treasure his letter and the memory of this great and saintly man.

*****

*****

from the Jérôme Lejeune Foundation:

In 1958, Professor Jérôme Lejeune, a doctor and researcher at the Necker Hospital in Paris, discovered an extra chromosome on the 21st pair and in so doing discovered the genetic cause of Down syndrome. As the father of modern genetics, he received may international awards for his work, including the Kennedy Prize and the Allen Memorial Award.

Trisomy 21 (Down Syndrome) is not a fatal condition, but a disability caused by a genetic error at conception and the most common single cause of birth defects in humans. Professor Lejeune was convinced that one day researchers would discover treatments that would largely restore the intellectual capabilities of individuals born with Down syndrome. The Jérôme Lejeune Foundation is committed to fulfilling Professor Lejeune’s dream, and in collaboration with researchers around the world conducts and funds research leading to targeted treatments to address issues related to cognition, memory, and speech, as well as the other comorbidities caused by the extra 21st chromosome.
Every year the Jérôme Lejeune Foundation provides funding to over 60 research teams who are pursuing treatments for genetic intellectual disabilities in the US, Canada, France, Israel, Italy, Lebanon, Spain, Switzerland, the UK, and other countries. The Foundation is the world’s oldest and largest funder of research to find treatments for Trisomy 21 and other genetic intellectual disabilities. Our grants are 100% funded by private donations.
The Foundation also supports clinical research through the the Institut Jérôme Lejeune, in Paris, such as the ACTHYF program which aims to establish a link between the use of folinic acid and thyroid hormone to improve the psychomotor development of toddlers with Down syndrome. The Institute offers lifelong, specialized medical care through a medical and paramedical team. The Institut Jérôme Lejeune treats over 3,600 patients annually from France and abroad.
All of the Jérôme Lejeune Foundation and its subsidiaries’ work has an ethical label which ensures the utmost respect for the value of each and every human life. The Foundation will only finance research that respects human life from conception to natural death. We do not support any projects that use products derived from human embryos or fetuses as research material.

****

from the Down Syndrome Radio Podcast:
Our guest on this episode of the podcast is Mark Bradford, President of the Jérôme Lejeune Foundation, USA.  I had the pleasure of meeting Mark at the kickoff event for the Race Across America.  He is the Down Right Awesome Dad of seven children.  We probably could have spent the entire hour discussing how one handles seven kids, but the work being done by the Lejeune Foundation is so interesting we’ll have to save that topic for another show.  Mark gives us some history of Dr. Lejeune and the foundation that bears his name.  We also discuss how the foundation strives to achieve the three fundamental points of its mission.
Download Down Syndrome Radio, Episode #9 or listen via iTunes

Scientists make stunning inner space observations

from Science Codex by University of Leicester:

Scientists using high-powered microscopes have made a stunning observation of the architecture within a cell – and identified for the first time how the architecture changes during the formation of gametes, also known as sex cells, in order to successfully complete the process.

The findings by the international team led by the University of Leicester could impact on the treatment of disorders caused by a misregulation of cellular structures called microtubules. These disorders include Down syndrome, lissencephaly (a brain formation disorder) or cancer.

By exploiting yeast cells, the researchers have discovered for the first time the precise structure adopted by microtubules, which play a vital role in the process of gamete formation, and identified the protein responsible for creating the structure. They further found that the protein needs to be regulated in order to complete gamete formation, failure of which may lead to production of gametes with the wrong number of chromosomes. In humans, these may contribute to disorders such as Down sydrome that result from chromosomal abnormalities.

Research links cancer cells & cognitive deficits in Down syndrome

From EurekAlert.org:

Dana-Farber Cancer Institute scientists have discovered new details of how cancer cells escape from tumor suppression mechanisms that normally prevent these damaged cells from multiplying. They also demonstrated a potential link between this cell proliferation control mechanism and the cognitive deficits caused by Down syndrome.

James A. DeCaprio, MD, of Dana-Farber said the results may provide new targets both for blocking the progress of cancer and perhaps for facilitating the growth of neurons in the developing brains of infants with Down syndrome.

DYRK1A's ability to turn off cell growth genes may also be involved in the lower-than-normal development of brain neurons in Down syndrome, say the scientists, who are investigating possible new avenues to treating the disorder.

While they tend to have cognitive losses, people with Down syndrome have a markedly lower risk of most types of cancer. DYRK1A is made by a gene on chromosome 21, which is present in three copies instead of the normal two in people with Down syndrome, causing the enzyme to be overproduced. DeCaprio said this abnormal activity could explain both outcomes: DYRKIA-triggered DREAM formation could help suppress cancers by driving them into senescence, and also reduce the generation of brain cells during development.