Changing Minds Workshop

Watch this short tv segment from Evansville, Indiana. Miriam Kauk, the parent of a child with Down syndrome, is promoting an upcoming seminar for the Changing Minds Foundation. Dr. Teresa Cody will be speaking about the Changing Minds protocol and the amazing results that parents, teachers and doctors are seeing in people with DS. The event is sponsored by SMILE On Down Syndrome, a parent organization in Evansville, IN, for parents with loved ones that have Down syndrome.

Changing Minds Workshop

Sleep and the GABA Receptor

I found a remarkable study out of the University of McGill in Montreal, Canada.

 "Dynamic changes in GABA A receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery"

          "These changes in membrane GABA receptors would be associated with increased GABA-mediated inhibition of cholinergic cells following prolonged waking and diminished inhibition following sleep and could thus reflect a homeostatic process regulating cholinergic cell activity and thereby indirectly cortical activity across the sleep-waking cycle."

OK, Ok translation...... They measured the number of GABA receptors on the cell membrane and found that the number of receptors on the membrane changes when the subject is either sleep deprived or rested. They actually stained the GABA receptors sitting on the membrane. Here is a picture of the GABA receptor (the yellow thing) sitting  ON the membrane:



The little yellow things are the GABA A receptors. But the most interesting part is that they circulate in and out of the membrane. They are picked up by a little 'submarine' and brought inside the cell.  Here is a picture of the GABA receptors and the submarines:



Now why do we care? Well let's get back to the study above. They found that if the animal was sleep deprived there were many GABA receptors sitting on the membrane. But if the animal was rested, the GABA receptors were inside the cell (postsynaptic neuron) in the submarine. Here is a picture of that:

Again, why do we care? Because the submarine in Down syndrome does not work well. Down syndrome end up with GABA receptors on the membrane longer than normal. Are we in a constant state of sleep deprivation?
Tomorrow we will review the consequences of having the GABA receptor on the membrane too long.




         



Neal's Work With REM Sleep

I thought this was pretty good? What do you think?

I really can't wait to show you what he is able to do in 3 or 4 months of 'sleeping'.

I came home yesterday to find these worksheets Neal had done with his tutor. This is tough stuff. His tutor always writes on the paper whether he has done the  work by himself. I circled what the tutor commented in red.

Something Good to Share

Yesterday, Neal came home with a Valentine's that he colored for me and he colored a dragon. The dragon is his new pet but I was so impressed with his coloring. A couple of things have improved: 1) he used 4 different colors [usually he only uses 1 color] 2) he stayed in the lines. I scanned it in.
This is central and detailed vision. He keeps improving daily! [one little brag]

Choline Part 2

Tomorrow we will get back to the green tea extract and DYRK1 A gene because there are more issues to discuss but today let's look at one little study that showed positive results for the Down syndrome mouse.
Here is the study abstract:
Behav Neurosci. 2010 Jun;124(3):346-61.


Perinatal choline supplementation improves cognitive functioning and emotion regulation in the Ts65Dn mouse model of Down syndrome.
Moon J, Chen M, Gandhy SU, Strawderman M, Levitsky DA, Maclean KN, Strupp BJ.
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.

Abstract

In addition to mental retardation, individuals with Down syndrome (DS) also develop the neuropathological changes typical of Alzheimer's disease (AD) and the majority of these individuals exhibit dementia. The Ts65Dn mouse model of DS exhibits key features of these disorders, including early degeneration of cholinergic basal forebrain (CBF) neurons and impairments in functions dependent on the two CBF projection systems; namely, attention and explicit memory. Herein, we demonstrate that supplementing the maternal diet with excess choline during pregnancy and lactation dramatically improved attentional function of the adult trisomic offspring. Specifically, the adult offspring of choline-supplemented Ts65Dn dams performed significantly better than unsupplemented Ts65Dn mice on a series of 5 visual attention tasks, and in fact, on some tasks did not differ from the normosomic (2N) controls. A second area of dysfunction in the trisomic animals, heightened reactivity to committing an error, was partially normalized by the early choline supplementation. The 2N littermates also benefited from increased maternal choline intake on 1 attention task. These findings collectively suggest that perinatal choline supplementation might significantly lessen cognitive dysfunction in DS and reduce cognitive decline in related neurodegenerative disorders such as AD.


PMID: 20528079 [PubMed - indexed for MEDLINE]PMCID: PMC2955960 [Available on 2011/6/1]

They supplemented with choline which crosses the Blood Brain Barrier (protective barrier for the brain) with a transport system. Phosphatidylcholine (PC) passes through the BBB because it  is fat soluble. I'm always thinking about making it as easy as I can for the body. So, my choice of supplementation is PC as opposed to free choline.

Could It Be As Easy As Vitamin E?

Degeneration is a problem for all of us, but it is especially problematic in Down syndrome. It has been well established that loss of neurons is an enormous problem and leads to early decline in function. In the study below, they treated the DS mice with vitamin E. The antioxidant action of the vitamin E improved memory in the DS mice. This study is available free online.

Exp Neurol. 2009 Apr;216(2):278-89. Epub 2008 Dec 10.


Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model.

Lockrow J, Prakasam A, Huang P, Bimonte-Nelson H, Sambamurti K, Granholm AC.

Department of Neuroscience, and the Center on Aging, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.

Abstract

Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated oxidative stress in Ts65Dn mice, and assessed the efficacy of long-term antioxidant supplementation on memory and basal forebrain pathology. We report that oxidative stress was elevated in the adult Ts65Dn brain, and that supplementation with the antioxidant vitamin E effectively reduced these markers. Also, Ts65Dn mice receiving vitamin E exhibited improved performance on a spatial working memory task and showed an attenuation of cholinergic neuron pathology in the basal forebrain. This study provides evidence that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology.

PMID: 19135442 [PubMed - indexed for MEDLINE]PMCID: PMC2704550Free PMC Article

Validation for Treatment of the Mental Challenges in Down Syndrome

The following was written by Linda Blevins, one of Changing Minds Foundation's founding members. Her son with DS is 16 and been on treatment for 5 years.

Article written by: Linda Blevins
Choline improves Cognition in Down syndrome mice models.
The Changing Minds Foundation protocol is based upon scientific research. The newest research supports the CMF science based protocol for the treatment of cognitive challenges in Down syndrome.
CMF protocol recommends the use of phosphotidyle choline (PC) rather than just plain choline. PC is more potent and is the active form the body needs. The link to the CMF web site explains more about PC. http://www.changingmindsfoundation.org/documents/phosphatidyl_choline.html

A number of scientific studies have vailidated the CMF protocol which targets critical cycles that function poorly in Down syndrome. These cycles produce invaluable neurotransmitters that are needed for learning, focus, attention, memory production and growing neurons for connection and signalling. (Who doesn't think that's important???)..Though sometimes we don't appreciate the new behaviors that come from growing a brain. Yet, I love the educational progress. Jordan's current school lessons examples:

--Spelling words: several, grumble, putrid

--Vocabulary words: etiquette, obnoxious
Linda Blevins

 Science News

http://www.sciencedaily.com/releases/2010/06/100603132456.htm

More Choline for Pregnant, Nursing Women Could Reduce Down Syndrome Dysfunction, Guard Against Dementia

ScienceDaily (June 4, 2010) — More choline during pregnancy and nursing could provide lasting cognitive and emotional benefits to individuals with Down syndrome and protect against neurodegenerative conditions such as Alzheimer's disease, suggests a new Cornell study of mice.
The findings, published June 2 in Behavioral Neuroscience, could help lead to increasing the maternal dietary recommendations for choline (currently 450 milligrams a day during pregnancy, 550 milligrams for lactation), a nutrient found in egg yolks, liver, nuts and such vegetables as broccoli and cauliflower.

"We found that supplementing the maternal diet with additional choline resulted in dramatic improvements in attention and some normalization of emotion regulation in a mouse model of Down syndrome," said lead author Barbara Strupp, professor of nutritional sciences and of psychology. The researchers also found evidence for "subtle, but statistically significant, improvement in learning ability in the non-Down syndrome littermates."

In addition to mental retardation, Down syndrome individuals often experience dementia in middle age as a result of brain neuron atrophy similar to that suffered by people with Alzheimer's disease. Strupp noted that the improved mental abilities found in the Down syndrome mice following maternal choline supplements could indicate protection from such neurodegeneration "in the population at large."

Strupp and her co-authors tested Down syndrome model mice born from mothers fed a normal diet and those given choline supplements during their three-week pregnancy and three-week lactation period, as well as normal mice born from mothers with and without additional choline. The choline-supplemented mothers received approximately 4.5 times more choline (roughly comparable to levels at the higher range of human intake) than unsupplemented mothers.

At six months of age, the mice performed a series of behavioral tasks for about six months to assess their impulsivity, attention span, emotion control and other mental abilities.

In addition to dramatic improvements in attention, the researchers found that the unsupplemented Down syndrome model mice became more agitated after a mistake than normal mice, jumping repeatedly and taking longer to initiate the next trial, whereas the choline-supplemented Down syndrome model mice showed partial improvement in these areas.

"I'm impressed by the magnitude of the cognitive benefits seen in the Down syndrome model mice," Strupp said. "Moreover, these are clearly lasting cognitive improvements, seen many months after the period of choline supplementation."

Strupp noted that the results are consistent with studies by other researchers that found increased maternal choline intake improves offspring cognitive abilities in rats. However, this is the first study to evaluate the effects of maternal choline supplementation in a rodent model of Down syndrome. This is also one of the few studies that has evaluated offspring attentional function and effects in mice, rather than rats, Strupp noted.

Previous studies of humans and laboratory animals have shown that supplementing the diets of adults with choline has proven to be largely ineffective in improving cognition. "Although the precise mechanism is unknown, these lasting beneficial effects of choline observed in the present study are likely to be limited to increased intake during very early development," Strupp said.

The study, funded in part by the National Institutes of Health (NIH), was part of the dissertation of Jisook Moon, Ph.D. '06. Other Cornell collaborators included Myla Strawderman, research associate in nutritional sciences; David Levitsky, professor of nutrition and of psychology; May Chen '07 and Shruti Gandhy '07.

Strupp and collaborators have received additional NIH funding to study the neural mechanisms underlying the positive cognitive effects of perinatal choline supplementation observed in this study.

Our Biggest Supporters Come In Small Packages

The 'Spare Change for Changing Minds' campaign is catching on. Meet Ally, one of our best fundraisers.  Her mother, Kari, works in my office and she brought a can home to help support Changing Minds.  Ally took the initiative and went door to door in her neighborhood to collect money.  She filled her can in no time!  If you remember in an earlier blog, Reid had collected money for us too.  It looks like the kiddos are CMF's strongest supporters !!!!  Thank you Ally for being willing to ask your friends and neighbors for their "spare change".  We are getting closer to our goal of funding more research into treatments for Down syndrome.

Cure Down Syndrome Now

If I read one more time that Down syndrome can't be cured because it is a chromosome disorder, I will scream!!!!!!

Why did we get shoved into that box?

Rett syndrome is a chromosome disorder.

Go to the Rett syndrome website

"The core mission of the IRSF (International Rett Syndrome Foundation) is to fund research for treatments and a cure for Rett syndrome while enhancing the overall quality of life for those living with Rett syndrome by providing information, programs, and services."

Fragile X is a chromosome disorder.

FRAXA is a nonprofit organization run by parents. Our mission: to find treatments and a cure for Fragile X by funding the most promising research. FRAXA has funded $18 million in research.

Prader-Willi syndrome is a chromosome disorder.

There logo is below:

AAAAaaaaaggghhhhh!!!!

Everyone gets a CURE but Down Syndrome!!!

We should at least try!!!!!!!!!!!

Press Release written by Patricia Almeida

The Changing Minds Foundation (CMF) held its first Conference on July 23-24, in Houston, TX, to discuss available treatments for the different intellectual disabilities that affect persons with Down syndrome and to present the ongoing research at Stanford University Down Syndrome Center.
Various testimonies of families and professionals, who work with those using the Changing Minds Protocol, were presented, as well as, findings from researchers at Stanford University that investigate drugs to enhance memory and learning in individuals with Down syndrome by testing on the DS mouse model.
The Changing Minds Protocol was established by Teresa Cody DDS, the mother of a child with DS. Teresa worked with other mothers around the world via email and they researched the Internet to find an array of scientific studies. The studies using DS mouse models showed improvement in the mouse's ability to learn and remember. The protocol, that uses FDA approved medicines includes, B 12, Folic Acid, Ginkgo Biloba, Prozac (Fluoxetine), Phosphatidylcholine, Body Bio Balanced Oil and Focalin XR (or another ADHD medication).
Changing Minds Foundation estimates that around 200 families use the CMF protocol worldwide, or at least parts of it, and the large majority of these families have observed great advances in their child's development with no appreciable side effects. According to some presenters, some children have started the medicines as young as 3 months old and have been showing signs of development of a typical child. Pictures and videos of the treated children were shown to illustrate improvements.
Joanne Mothes, a teacher with 38 years of experience tutors 30 pupils with Down syndrome in Columbus Ohio. 14 of them are on the CMF protocol and 16 are not. She said that the difference between the two groups is remarkable. The title of her talk was 'Draw a line in the Sand'. According to Joanne, children that use the protocol are more attentive, more verbal, learn faster, and remember what they learn. She also said she noticed good results comparing the students to themselves, before and after starting the CMF protocol.
Research:
Scientists from Stanford University Down Syndrome Research Center, Craig Heller, PhD., Craig Garner, PhD, and Dan Wetmore, PhD talked about their research using PTZ (Pentylenetetrazol) and how that drug had similar effects to Ginkgo Biloba, which is currently being used in the CMF protocol. It acts on the GABA receptors of the cell, controlling the balance between excitation and inhibition, aiming to regulate these 2 stimuli, that are out of balance in mice and presumably individuals with Down syndrome. As the researchers described, too much inhibition can lead to retardation and even coma, while excess excitation can cause hyperactivity to seizures. Drs. Heller, Garner and Wetmore all affirmed that this research is advanced, but it will take time and funds to carry out clinical trials on PTZ. At this time, they estimate that it will take 10 years to get FDA approval.
The Stanford team, as well as, other participants of the conference, stressed the need for families to engage in fundraising and applying political pressure in order to implement more research. They also pointed out that it is crucial that the medical community, especially pediatric, psychiatric and neurological physicians be informed and get involved by working with patients that wish to use the treatments already available.
More information: http://www.changingmindsfoundation.org
http://dsresearch.stanford.edu

Balancing Brain Chemistry

The idea that there is a cure for Down syndrome bothers some people. Over the weekend, I read a few blogs that say that we cannot remove the extra chromosome from every cell, therefore there cannot be a cure for Down syndrome. It is not about removing an extra chromosome -- our medicine doesn't do that for any medical problem. We treat the symptoms.

What the latest study from Stanford University showed is that 'balancing the brain chemistry', changed how the mice could perform. Treatment or cure for Down syndrome is all about balancing the brain chemistry. But if you think about it, balancing brain chemistry is exactly what psychiatric medicine has evolved into. At one time, you went to the doctor to talk about your problems. Now, you describe a symptom and you are given a prescription to balance the chemistry. It may take some trial and error to get it right, but researchers don't have a mouse model of you. That is where Down syndrome is lucky. They have a little mouse that can help explain what is going on inside their heads.

The other argument against treatment for Down syndrome is that there have not been clinical trials using these psychiatric agents. I would point out that there have not been clinical trials using any medicine commonly given to kids and adults with Down syndrome.

For example, we use antibiotics with Down syndrome and we know they have compromised immune systems. Would we demand a clinical trial before we gave our child Amoxicillin if they had an infection? No, we would just assume that the DS child is similar enough to the average child to safely use the antibiotic.

Have there been clinical trials on the reflux medicine that we give our Down syndrome children? No. Does that stop us from treating the reflux? No.

Have there been clinical trials on ibuprofen or Tylenol that we give our Down syndrome children? No. Does that stop us from giving those medications when they are needed? No.

I looked up clinical trials in Down syndrome and found a vitamin E study, Donepezil (an Alzheimer drug), antioxidant vitamin study, and some growth and thyroid hormone studies.

So, only when we move to try to treat the source of the difficulties is a clinical trial brought up. The source of the slow processing is the brain. The source of the low motor skills is the brain. The source of the low verbal skills is the brain. The source of the poor memory is the brain.

Dr. Craig Garner at Stanford University has been working on the cause of the poor memory in Down syndrome. We now know it is a little receptor called a GABA receptor. Without any treatment the receptor is stuck in the open position in Down syndrome. With some simple chemistry, the receptor can be rebalanced to open and close more normally. This simple chemistry balances the brain chemistry.

Dr. Salahi at Stanford found that the level of norepinephrine is low in subjects with Down syndrome. A common way to restore norepinephrine levels to a more normal level is ADHD medicine.

Dr. Mobley found that the transport system for Nerve Growth Factor was broken so the nerves did not get this necessary support. But when they added it to the nerves, they restarted as if they are lying dormant. To our benefit, a medicine as common as Prozac has been shown to increase another nerve factor chemical (BDNF). This is a fairly easy way to compensate for the brain chemistry imbalance.

Balancing brain chemistry is not new. Many of our friends and loved ones struggle with depression and other brain chemistry imbalances. We understand how they can be helped with the correct medicine. The situation in Down syndrome is the exact same thing; it is a matter of balancing brain chemistry to proper levels.

Myth: Down syndrome can never be cured.
Truth: Research on Down syndrome is making great strides in identifying the genes on chromosome 21 that cause the characteristics of Down syndrome. Scientists now feel strongly that it will be possible to improve, correct or prevent many of the problems associated with Down syndrome in the future.

Who said this?

A few years ago, I named a website 'Cure Down syndrome' and was chastised for it. I literally got hate emails. How dare you say cure in connection with Down syndrome. There is nothing to cure, is what the emails argued.

I named it that on purpose, to see what would happen. Now, five years later, the big boys have it on their website. Granted it is all the way down at the bottom of the page, but it is written in black and white.

Have you guessed yet?

The truth is I'm very happy they are saying the word cure. The definition of cure is: Cure: 1. To heal, to make well, to restore to good health.

Who doesn't want good health?

There are definable problems with Down syndrome and to restore these problems to a more normal, healthy function is a good thing. For example, increasing the ability to learn is a good thing. The Changing Minds Foundation is dedicated to improving learning and memory through modern medicine. It is as simple as restoring functions in the brain to a more normal level. So, is it a cure?

The only problem with the word cure is that people seem to think it means to eliminate the problem in its entirety. So, a person with Down syndrome is only cured if the chromosome is completely removed from every cell. But this is not the true meaning at all. Cured means to restore to good health.

Someone is cured of cancer when the symptoms of cancer are gone, not when the cause of the cancer is eliminated. Many cancers, for example, are due to genetic causes. Hence, the question by the doctor about your family history. They don't ask because they are interested in genealogy. Your family history is important to your future health because of the genes you may carry.

So, who was it that made this statement?

Myth: Down syndrome can never be cured.
Truth: Research on Down syndrome is making great strides in identifying the genes on chromosome 21 that cause the characteristics of Down syndrome. Scientists now feel strongly that it will be possible to improve, correct or prevent many of the problems associated with Down syndrome in the future.

It was on the NDSS, the National Down Syndrome Society's website.

http://www.ndss.org/index.php?option=com_content&view=article&id=59&Itemid=76

The only difference between NDSS and CMF is we think the future is now. Thank you to all the dedicated research scientists for making the future NOW.