Interesting Research done at University of Washington

Extra chromosome 21 removed from Down syndrome cell line

University of Washington scientists have succeeded in removing the extra copy of chromosome 21 in cell cultures derived from a person with Down syndrome, a condition in which the body’s cells contain three copies of chromosome 21 rather than the usual pair.

A triplicate of any chromosome is a serious genetic abnormality called a trisomy. Trisomies account for almost one-quarter of pregnancy loss from spontaneous miscarriages, according to the research team. Besides Down syndrome (trisomy 21), some other human trisomies are extra Y or X chromosomes, and Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), both of which have extremely high newborn fatality rates.

In their report appearing in the Nov. 2 edition of Cell Stem Cell, a team led by Dr. Li B. Li of the UW Department of Medicine described how they corrected trisomy 21 in human cell lines they grew in the lab.  The senior scientists on the project were gene therapy researchers Dr. David W. Russell, professor of medicine and biochemistry, and Dr. Thalia Papayannopoulou, professor of medicine.

The targeted removal of a human trisomy, they noted, could have both clinical and research applications.

In live births, Down syndrome is the most frequent trisomy. The condition has characteristic eye, facial and hand features, and can cause many medical problems, including heart defects, impaired intellect, premature aging and dementia, and certain forms of leukemia, a type of blood cancer.

“We are certainly not proposing that the method we describe would lead to a treatment for Down syndrome,” Russell said.  “What we are looking at is the possibility that medical scientists could create cell therapies for some of the blood-forming disorders that accompany Down syndrome.”

For example, he said, someday Down syndrome leukemia patients might have stem cells derived their own cells, and have the trisomy corrected in these lab-cultured cells.  They could then receive a transplant of their own stem cells – minus the extra chromosome – or healthy blood cells created from their fixed stem cells and that therefore don’t promote leukemia, as part of their cancer care.

He added that the ability to generate stem cells with and without trisomy 21 from the same person could lead to better understanding of how problems tied to Down syndrome originate.  The cell lines would be genetically identical, except for the extra chromosome. Researcher could contrast, for example how the two cell lines formed brain nerve cells, to learn the effects of trisomy 21 on neuron development, which might offer insights into the lifelong cognitive impairments and adulthood mental decline of Down syndrome. Similar comparative approaches could seek the underpinnings of untimely aging or defective heart tissue in this genetic condition.

The formation of trisomies is also a problem in regenerative medicine research using stem cells. Russell and his team observed that their approach could also be used to revert the unwanted trisomies that often arise in creating stem cell cultures.

Figuring out the exact techniques for removing the extra chromosome was tricky, Russell said, but his colleague Li worked hard to solve several challenges during his first attempts at deriving the engineered cell lines.

“Dr. Li’s achievement was a tour de force,” Russell said.

The researchers used an adeno-associated virus as a vehicle to deliver a foreign gene called TKNEO into a particular spot on chromosome 21, precisely within a gene called APP, which sits on the long arm of the chromosome.  The TKNEO transgene was chosen because of its predicted response to positive and negative selection in specific laboratory growth mediums.  When grown in conditions that selected against TKNEO, the most common reason for cells to survive was the spontaneous loss of the chromosome 21 harboring the transferred gene. Other survival tactics were point mutations, which are single, tiny alterations in DNA base pairs; gene silencing, which meant TKNEO was “turned off” by the cell; or deletion of the TKNEO.

Russell explained a key advantage of this technique for getting rid of the entire extra chromosome: Once it was gone, nothing was left behind.

“Gene therapy researchers have to be careful that their approaches do not cause gene toxicity,” he said. This means, for example, that removal of a chromosome must not break or rearrange the remaining genetic code. This method shouldn’t do that.”

Other researchers on this study were Kai-Hsin Chang, Pei-Rong Wang and Roli K. Hirata. The project was supported by grants from Horizon Discovery and from the National Institutes of Health (DK55759, HL53750,GM086497, DK077864, and HL46557.)  The researchers declared no financial conflicts of interest.


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Dr. Julia Kinder & A Petition to Medical Schools

I received an email about 10 days ago and just kept forgetting to look at it with much detail. I took a look at it today and while it's not Down Syndrome Awareness Month still, thought it would be good to share nonetheless. 

Celebrate the UPside of Down™ during National Down Syndrome

Awareness Month: Dispelling Myths and Smashing Stereotypes

Dr. Julia Kinder is celebrating National Down Syndrome Awareness Month with a Sweepstakes,

Photo Contest, and a Petition to Medical School Faculty across the United States.

Cape Girardeau, MO – October 18, 2012 – Dr. Julia Kinder, practicing physician, national speaker, and an advocate for children with special needs, is celebrating National Down Syndrome Awareness Month with an online Photo Contest, Sweepstakes, and a very important Petition. These can be found on her website, www.JuliaKinder.com. The photo contest gives families of children with Down syndrome an avenue for showcasing their child’s abilities. The sweepstakes offers fun awareness products created by Dr. Kinder while drawing attention to dispelling the myths and stereotypes surrounding Down syndrome.  The newly launched petition calls upon medical schools to provide more training on Down syndrome.

“No parent should feel like their baby's life starts out with a death; the death of their dreams for the future, the end of their hope for a happy, healthy child,” said Dr. Kinder, owner of JuliaKinder.com. “But it happens every day, because physicians who deliver the diagnosis of Down syndrome often give inaccurate, incomplete, and negative information that intensifies the unfounded fear of this diagnosis.”

Currently physicians do not receive training on giving the diagnosis of Down syndrome in a productive way, according to Dr. Kinder. Nor do they learn of needed resources for parents and baby. Medical education focuses on the possible health and learning issues, which not every child will encounter. Physicians do not understand what a child with Down syndrome is like outside of the medical aspects. What is crucial to every baby with Down syndrome is that they begin receiving early intervention and therapy immediately. Medical education does not cover this topic, therefore, physicians are missing a crucial piece of information to pass along to new parents.

Dr. Kinder has been a practicing physician for the past decade. However, eight years ago when her daughter was born with Down syndrome, she discovered her medical training did nothing to prepare her for raising a child with Down syndrome.

“Ella is completely healthy and smart, which contradicts everything I learned about Down syndrome,” said Dr. Kinder. “Medical school taught me about a laundry list of health problems and mental retardation, none of which applied to my child. I had no practical information on how to take care of her. I didn’t know she needed to start therapy immediately. When she was born, the doctors and hospital gave me no information or resources. I left the hospital without so much as a pamphlet.”

According to Dr. Kinder, the information on Down syndrome that doctors give to new parents tends to focus on the potential medical and learning problems. Doctors have not been trained to explain to these new parents that a child with Down syndrome is more like other children than they are different, and that many of the medical issues never materialize. Parents leave the hospital with the impression that their child’s prospects for a happy, healthy, and fulfilled life are grim. Unfortunately, many parents admit they struggled to connect emotionally with their baby during those first few months, as if unconsciously attempting to prepare for some awful manifestation of the diagnosis.

“I have decided to tackle this issue head-on,” states Dr. Kinder. “It is unacceptable for the medical community to contribute to a new parent’s fear of their own baby. This negative emotional state can prevent parents from providing the appropriate care their newborn needs. Babies with Down syndrome must start early intervention and therapy immediately - it should not be delayed because doctors fail to give parents complete and accurate information, along with resources for support.”

Dr. Kinder has spent eight years speaking to the medical community, future teachers and therapists, and to the general public regarding Down syndrome, as well as counseled hundreds of new parents. In 2009 Dr. Kinder began blogging on the topic, giving new parents hope and direction. She has devised fun ways to dispel the myths and darkness by promoting positive phrases such as “My kid has more Chromosomes than yours” as well as the “UPside of Down” concept. She encourages others to proudly display the UPside of Down with car decals, shirts, bracelets, and other awareness products that she has developed. Dr. Kinder has created a tribe of families who support each other and spread awareness. Their motto is, “Go beyond just surviving [with Down syndrome] to Thriving - become a Thrivalist!”

“I want to show the world the UPside of Down syndrome and I want to improve the education medical students receive on helping new parents,” said Dr. Kinder. “My ultimate goal is for the birth of every baby with Down syndrome to be celebrated, and for every baby to receive the care required to maximize their developmental potential.”

To get involved and sign Dr. Kinder’s petition please go to www.JuliaKinder.com/petition/. To learn more about her website’s Down Syndrome Awareness Month activities and to participate in the celebration, please visit http://www.JuliaKinder.com/DownSyndromeCelebration/.

About Dr. Julia Kinder

Dr. Julia A. Pewitt Kinder is an accomplished national speaker, early childhood education advocate, author and practicing physician. She and husband Mitch reside in Cape Girardeau, Mo., with their three children, Ella and twin boys Paxton and Dexter.  Dr. Kinder is licensed to practice in both Missouri and Texas and is in private practice with her brother in Jackson, Missouri. She also serves as a hospice physician for Tri-County Hospice. In addition, Dr. Kinder is a certified fitness instructor and promotes easy ways to incorporate exercise into daily routines. More information about Dr. Kinder can be found on her website at www.JuliaKinder.com.

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31 for 21: Oxidative Stress & Down Syndrome

Well, 31 for 21 is coming to a close. I didn't get nearly as many "in-depth" posts up as I may have liked. So, I'll just have to work on that over the next few months :).

Today, I wanted to share a study that came across a DS listserv the other day on Oxidative Stress and Down syndrome.

Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia

You can view the full text of the report here.

I wanted to point out a few quotes from the conclusion.

It's already a well established fact that there is increased oxidative stress in Down syndrome, just like this points out.

"Within the context of the reported findings discussed above, we hypothesize that trisomy affects gene/protein expression that results in increased OS conditions and impaired mitochondrial function. These alterations occur early in DS as demonstrated by studies performed on fetal brain and amniotic fluid from DS pregnancy and play an important  role in neurodegeneration."

This is true below and a lot of people may not realize it. It's not just that the overexpression of SOD1 causes increased oxidative stress. It also reduces levels of agents that would counter act that oxidative stress and lowers the antioxidant enzymes.

"OS conditions arise not only from overexpression of SOD1 but also as a consequence of low levels of reducing agents and antioxidant enzymes."

Just thought this was an interesting statement:

"It is now well accepted that OS contribute to neurodegeneration, but in the case of DS and AD, genetic similarities, due to the fact that some of the genes responsible for familial form of AD are encoded by Chr21, provide an interesting field of research for the comprehension of many yet unsolved issues."

This is exactly why targeted nutritional intervention is so entirely important for individuals with DS. We have to combat the low antioxidant levels in DS with plenty of antioxidants!

"Based on this notion, it is possible that using antioxidant nutrients to scavenge oxygen-derived free radicals may modulate some of the complications of DS. "

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31 for 21: Life On The Ranch, Last Night with the Grandparents

Today was the last day for my Granny from California with her 3 week visit. So, a few of us had to go drop her off at the airport. My other grandparents from California will be leaving soon also, so it was time to spend the last little while with them before they left also. That meant we had a family BBQ tonight.

It was a beautiful, still night, perfect temperature, with a full moon and a great time around the campfire. Truly blessed and thankful!

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31 for 21: Getting late

Well, it's getting late here and I just want to get a post up for the night. Grandparents have been here for almost a month and will be leaving soon. We attended a debate tonight with our congressional candidates.

The fall weather is nice and so I'll just share a few pictures for tonight!

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31 for 21: The "R" Word Controversy

Being in the special needs community for almost 8 years now, I am fully aware of all the 'Politically Correct' lingo that should be used. You know, you say "a child with Down syndrome", not a "Down syndrome child." And there are also certain words which just are not supposed to be said, the word "retard" being at the top of the list.

It took some getting used to for me, because my family has never been very "politically correct" :).

Over the years I've seen the issues that come up when certain popular individuals use the "R" word, when someone who has a child with DS has a friend say this word in a conversation, or when it's use is discussed on a forum. I've never said much about it, because I think a lot of people will have a problem with my view on it.

Last week though, Ann Coulter called President Obama a "retard" on Twitter. There has been a ton of outrage over her use of the "R" word. So, I feel it's time that I say something. I fully expect people to disagree with me, but I'm completely fine with that.

First and foremost, the First Amendment to the Constitution gives us, as Americans, freedom of speech. We should all have the freedom to use whatever words we want to. If someone is offended by a word, then apologize. But it should not be turned into this national campaign to "ban" the use of certain words. That's simply against the first amendment.

When people go on "campaigns" to stop the use of a word, promote "gay rights", advocate for "women's rights", etc, it becomes something that is part of the problem that our nation is in - people thinking that government is the answer.

Besides the above reasons as to why the "R" word should not be an issue, let's look at a little more technical things.

What is the definition of the word "retard"? According to Merriam-Websters it is:

to make slow; delay the development or progress of (an action, process, etc.); hinder or impede.

When I think of this word, I think of it's true meaning. Just like the medical books will use it for "retarded growth" (slow growth) or "mental retardation" (slow mental development).

 I wonder if people who have children with Down syndrome get so upset about the use of this word, because they don't want to accept the fact that their child with Down syndrome does learn at a slower level? Or often times do grow/mature at a slower rate? I know full well that my brother, O, learns at a much slower pace than his twin sister who does not have DS. Is there something bad about that? No, not at all.

Another way people explain this word is that it refers to individuals with a lower I.Q. This again brings me to the point above. If my brother has a lower I.Q., does it matter? No, it doesn't. Just because someone may have a lower I.Q. does not mean they are stupid.

I've often heard that if someone says the word "retard," they are insulting your child or loved one with DS because they are calling them "stupid" or "worthless." You know what, I don't think so. I don't view my brother with DS as "stupid" or "worthless," so I don't even equate that to him. Just because someone uses this word that has been used in correlation with special needs in a way other than the proper use, does not mean they are "putting down" someone with special needs.

Not that I am defending Ann Coulter here at all, but I think she brought up an interesting point when she was discussing this on the Piers Morgan show. I have no problem with the word "retard" being used with the definition above. Languages do change though, so *if* the word does not mean the above definition (I'm not saying it does), and society has changed it to meaning "loser", then let go of the word. It's not applying to your child. It's being applied to something totally different!

There's been a few times over the years that I or my family have encountered someone using the "R" word in their conversation with us. What do we do with it? Do we get all angry or tweaked out about it? No, we use it as a chance to educate them. We make it a light thing, because I don't want them to feel bad for using the word around me, because it doesn't offend me. We tell them it does offend a lot of people. And we also tell them the actual meaning of the word (slow) and how it's not really that bad of a thing.

Do I go around saying the word all the time? No, because I know it causes great offense in the special needs community.

My brother is not stupid. He's a smart little guy, even though he may have a lower I.Q. (could care less about I.Q. tests though) or learn things at a slower rate.

Bottom line though, I think people need to be less sensitive. It's simply a word.  When people read into the motives as to why an individual would use a certain word (to hurt the special needs community), it gets us into all sorts of problems.

Let the word go. Don't let it offend you. Educate people.



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31 for 21: Full day.

Well, I have a few topics I'd like to blog about, but it's getting super late, so it'll have to wait! I'll just share this video, which I've watched a few times and cried I think each time :(!




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31 for 21: Professor Feuerstein & a new Documentary on Down Syndrome

I received the following information from someone I know and I thought I would share it:
 

Professor Feuerstein from Israel is a psychologist who has helped many people.  Emily Kingsley, mother of Jason Kingsley, gives much credit to Professor Feuerstein and his teaching methods in helping her son who was born with Down syndrome progress and become a successful person.   She writes:  

Emily Perl Kingsley writes:

The self-sacrificing work of Professor Feuerstein to enhance the learning potential of children across the globe is legendary.  Now approaching 90 years of age, he has devoted a lifetime of service to children previously thought to be unteachable and has shown the world that all children can learn and become productive, contributing citizens.

Professor Feuerstein's innovative methods have been adopted world-wide and have revolutionized the way we think about children's potential to be mediated and taught.

I am grateful to the Professor on many levels.  My own son, who has Down syndrome, studied with Professor Feuerstein and while previously diagnosed as "profoundly retarded," went on to be able to achieve a full academic high school diploma and write and publish a book about his experiences growing up with Down syndrome.  I attribute this in very large part to the ability to think logically which he learned at the hand of Professor Feuerstein.  I believe that the work that he did with Professor Feuerstein was the most important educational work he ever did in his entire educational career.  The Professor literally taught my son how to think!

And my son is only one of thousands and thousands of children directly affected by Professor Feuerstein's remarkable techniques and amazing influence.

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31 for 21: New Study on Down Syndrome

OOPS! I missed yesterday's blog post and almost missed today's! I found a new study on PubMed and thought I'd post it up. Need to look into this study some more though.

Childs Nerv Syst. 2012 Oct 23. [Epub ahead of print]

Neurophysiologic intraoperative monitoring in children with Down syndrome.

Patel AJ, Agadi S, Thomas JG, Schmidt RJ, Hwang SW, Fulkerson DH, Glover CD, Jea A.

Source

Neuro-Spine Program, Division of Pediatric Neurosurgery, Texas Children's Hospital, Department of Neurosurgery, Baylor College of Medicine, 6621 Fannin Street, CCC 1230.01, 12th Floor, Houston, TX, 77030, USA.

Abstract

OBJECTIVE:

Neurophysiological monitoring during complex spine procedures may reduce risk of injury by providing feedback to the operating surgeon. This tool is a well-established and important surgical adjunct in adults, but clinical data in children are not well described. Moreover, to the best of our knowledge, neurophysiologic intraoperative monitoring data have not been reported in children with neurodevelopmental disorders, such as Down syndrome, who commonly present with craniocervical instability requiring internal fixation. The purpose of this study is to determine the reliability and safety of neurophysiologic intraoperative monitoring in a group of children with Down syndrome undergoing neurosurgical spine procedures.

METHODS:

A total of six consecutive spinal procedures in six children with Down syndrome (three boys and three girls; mean age 10 years, range 4-16 years) were analyzed between January 1, 2008 and June 31, 2011. Somatosensory evoked potentials were stimulated at the ulnar nerve and tibial nerve for upper and lower extremities, respectively, and recorded at Erb's point and the scalp. Motor evoked potentials were elicited by transcranial electrical stimulation and recorded at the extensor carpi ulnaris muscle and tibialis anterior muscle for upper and lower extremities, respectively. A standardized anesthesia protocol for monitoring consisted of a titrated propofol drip combined with bolus dosing of fentanyl or sufentanil.

RESULTS:

Somatosensory and motor evoked potentials were documented at the beginning and end of the procedure in all six patients. Changes during the surgery were recorded. Five patients maintained somatosensory potentials throughout surgery. One patient demonstrated a >10 % increase in latency or >50 % decrease in amplitude suggesting spinal cord dysfunction. A mean baseline stimulation threshold for motor evoked potentials of 485 + 85 V (range 387-600 V) was used. Four patients maintained motor evoked potentials throughout surgery. One patient had loss of left lower somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) after rod placement; upon removal of the rod, SSEPs returned but not MEPs. Another patient did not have consistent MEPs on one side and had absent MEPs on the contralateral side throughout the case. Loss of MEPs in these two patients did not correlate with postoperative neurological status. There were no complications directly related to neurophysiologic intraoperative monitoring technique.

CONCLUSIONS:

Neurophysiologic intraoperative monitoring during neurosurgical procedures in children with Down syndrome may be reliably and safely implemented. Changes in neurophysiologic parameters during surgery must be carefully interpreted, and discussed with the neurosurgeon, neurophysiologist, and neuroanesthesiologist, and may not correlate with postoperative clinical changes. These changes may be related to abnormal physiology rather than an insult at the time of surgery. Nonetheless, the authors advocate routine neurophysiologic intraoperative monitoring in this special group of children undergoing neurosurgical spine procedures.

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31 for 21: Just the Way You Are

I came across this music video a couple years ago and I thought it was so cute and sweet.

My brother is such a blessing just the way he is. With his extra chromosome. With his short, stubby little fingers. With his adorable and goofy smile. With his flexible legs (and arms). With his stop-and-smell-the-roses type of personality.

Very thankful for him.





 
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31 for 21: Fall Colors.

I know I've had one post with pictures after another. There are some more "in-depth" blog posts I have planned, but just haven't gotten to them yet. Maybe tomorrow or Wednesday.

Today we had dinner with the grandparents, but on the way we stopped to take some fall pictures along the road. Fall is so beautiful!

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31 for 21: DSAT Buddy Walk 2012

The DSAT buddy walk was today. It was the 10th annual walk, so it was a milestone walk. We had a great time with everyone. Erin & Alana did a fantastic job of getting it all together. It went so smooth and was great. I'll let the pictures tell most of the story. Enjoy!

 

 

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