Early Pharmacotherapy????

An outstanding piece of evidence emerged June of this year. Early treatment of the Down syndrome mouse "restores" cognitive performance. They didn't say "invents" cognitive performance. They say RESTORES. This implies that it is there waiting to be unleashed. And in fact, that is exactly what we observe with the children treated with the CMF protocol. The medicine unveils the awesome person inside.

The medicine used in this study was prozac (fluoxetine generic name). The nerves don't grow or develop properly in the memory area of the brain in Down syndrome. With early treatment with prozac, these DS mice had more normal brain development and had a complete recovery of memory task performance.

All I can say is WOW! We should be dancing on the rooftops and down on our knees thanking God. How easy is this. A known drug with 30 year history and cheap (as low as $3/ month at Walmart).
Watch John (5yo) in action who has been treated with prozac since he was 2 years old:
http://changingmindsfoundation.org/documents/videoblog.html

 Here is an abstract of the study mentioned above:

J Neurosci. 2010 Jun 30;30(26):8769-79.

Early pharmacotherapy restores neurogenesis and cognitive performance in the Ts65Dn mouse model for Down syndrome.
Bianchi P, Ciani E, Guidi S, Trazzi S, Felice D, Grossi G, Fernandez M, Giuliani A, Calzà L, Bartesaghi R.
Department of Human and General Physiology, University of Bologna, I-40126 Bologna, Italy.

Abstract
Down syndrome (DS) is a genetic pathology characterized by intellectual disability and brain hypotrophy. Widespread neurogenesis impairment characterizes the fetal and neonatal DS brain, strongly suggesting that this defect may be a major determinant of mental retardation. Our goal was to establish, in a mouse model for DS, whether early pharmacotherapy improves neurogenesis and cognitive behavior. Neonate Ts65Dn mice were treated from postnatal day (P) 3 to P15 with fluoxetine, an antidepressant that inhibits serotonin (5-HT) reuptake and increases proliferation in the adult Ts65Dn mouse (Clark et al., 2006). On P15, they received a BrdU injection and were killed after either 2 h or 1 month. Results showed that P15 Ts65Dn mice had notably defective proliferation in the hippocampal dentate gyrus, subventricular zone, striatum, and neocortex and that proliferation was completely rescued by fluoxetine. In the hippocampus of untreated P15 Ts65Dn mice, we found normal 5-HT levels but a lower expression of 5-HT1A receptors and brain-derived neurotrophic factor (BDNF). In Ts65Dn mice, fluoxetine treatment restored the expression of 5-HT1A receptors and BDNF. One month after cessation of treatment, there were more surviving cells in the dentate gyrus of Ts65Dn mice, more cells with a neuronal phenotype, more proliferating precursors, and more granule cells. These animals were tested for contextual fear conditioning, a hippocampus-dependent memory task, and exhibited a complete recovery of memory performance. Results show that early pharmacotherapy with a drug usable by humans can correct neurogenesis and behavioral impairment in a model for DS.



PMID: 20592198 [PubMed - indexed for MEDLINE]

Prozac Anyone?

Another study published June 2010 supports the use of Prozac in Down syndrome. Not only does it support the use of Prozac, it indicates Prozac should be started early, probably at birth. Maybe prenatally if you could.
The goal of the study was to see if early pharmacotherapy would improve neurogenesis and cognitive behavior. Guess what? It did.
Neurogenesis is literally what it sounds like. The birth of new neurons or nerves. It is now known that the ability to grow new nerves is a life long affair. At one time, it was believed that higher mammals (humans) did not have the ability to grow new neurons. It has come to light in the research world that we are not above new neurons. In fact, losing the ability to stimulate the growth of new neurons is what leads to depression and other neurodegenerative conditions.
Prozac has been on the market for 30 years. Over 55 million prescriptions have been written. If it had a terrible side effect, we would know. Stomach upset is the most common side effect. I get that from Mexican food.
I'm not making light of using drugs but my point is that weighing the options of degeneration versus regeneration, I'll take the regeneration, thank you.
The study looked at memory and learning in the Down syndrome mouse model. The DS mice did just as well as the typical mice in memory tests.

"These animals were tested for contextual fear conditioning, a hippocampus-dependent memory task, and exhibited a complete recovery of memory performance. Results show that early pharmacotherapy with a drug usable by humans can correct neurogenesis and behavioral impairment in a model for DS."

The abstract and full study is available online "Early Pharmacotherapy Restores Neurogenesis and Cognitive Performance in the Ts65Dn Mouse Model for Down Syndrome"
The thing we should be jumping up and down about is RESTORES COGNITIVE PERFORMANCE!!!!

Cure Down Syndrome? (Part 3)

Brain Problem 2:
Loss of neurons in the hippocampus (area of the brain where memories form):
Babies with Down syndrome lose 50% of their neuronal structure by 6 months of age. This seems like an insurmountable problem. In fetuses with Down syndrome, neurons fail to show normal dendritic development, yielding a “tree in winter” appearance. This developmental failure is thought to result in cognitive impairment.

Related Articles for Problem 2:
“Tree in winter” dendritic development
http://journals.lww.com/jneuropath/Abstract/2004/07000/Trisomy_21_and_the_Brain.1.aspx
2010 Prozac (Fluoxetine) Study
http://www.jneurosci.org/cgi/content/abstract/30/26/8769?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=fluoxetine+Renata+Bartesaghi&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
2006 Prozac (Fluoxetine) Study
http://www.ncbi.nlm.nih.gov/sites/pubmed/16624293?ordinalpos=1
2010 Prozac (Fluoxetine) Study
http://www.ncbi.nlm.nih.gov/pubmed/20592198
Additional Information about Prozac
http://www.changingmindsfoundation.org/documents/prozac.html

Remedy for Brain Problem 2:
In 2006, the University of Maryland School of Medicine treated Down syndrome mice with Prozac (generic name Fluoxetine). They discovered that Prozac treatment doubled the neuron count resulting in a normal level after 24 days. This is like increasing the hardware on your computer. It allows you to run more complicated software. Prozac received FDA approval in 2003 for ages 6 years and older. It seems clinically logical that people with Down syndrome could benefit from this drug because of the loss of neurons that occurs early and on an ongoing basis. Additionally, many people with Down syndrome commonly exhibit symptoms of anxiety and OCD early in life and depression later in life. Prozac can be used to address these issues as well. Participants as young as 10 months old are using the Prozac component of the protocol. Many young participants have been using Prozac for nearly 2 years without negative side effects.

Brain Problem 3:
Early onset Alzheimer Disease/Inflammation:
How do you lower the inflammatory markers safely and for a lifetime in a syndrome that represents an Alzheimer model?
Related Articles for Problem 3:
Phosphatidyl Choline
http://www.changingmindsfoundation.org/documents/phosphatidyl_choline.html
Omega 3, 6, 9 Oil
http://www.changingmindsfoundation.org/documents/body_bio_balanced_oil.html
Minocycline and Ts65Dn
http://www.ncbi.nlm.nih.gov/pubmed/15468085?ordinalpos=1&itool=EntrezSystem2.PEntrezPubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Inflammation Resolution and Lipids
http://www.ncbi.nlm.nih.gov/pubmed/19630766
Remedy for Brain Problem 3:
There is tremendous evidence that Alzheimer's disease is a state of chronic inflammation, specifically neuroinflammation. Inflammation is the body's natural response to injury or assault. It begins the healing process. There is a flip side to inflammation called resolution. Resolution is an 'active' process with specific chemicals that clears and limits the inflammatory response. A recent study from Harvard identified chemicals that reduce or control the magnitude of the inflammatory response. These chemicals are called Specialized Pro-resolving Mediators (SPM). These chemicals are derived from lipids, in other words, fatty acids – thus the importance of Body Bio Oil and Phosphatidyl Choline. You want your body to make these SPM's. SPM's include resolvins, protectins and maresins and are biosynthesized from essential omega-3 fatty acid precursors. The CMF's protocol aims to decrease inflammation by using fatty acids such as Phosphatidyl Choline (PC), Sunflower oil and Flaxseed oil. When used in the correct ratios they provide a safe, effective way to lower C-reactive protein, Interleukin 1 and Tumor Necrosis Factor which can contribute to inflammatory processes in the brain. Phosphatidyl Choline is a phospholipid that makes up 50%of the cell membrane. The membrane is the lining of every nerve cell that carries our signals. PC is a safe and essential fatty acid that studies have shown to protect the nerves from damage. Sunflower and Flaxseed oils are known for reducing inflammation by triggering a “restoration pathway.”
Brain Problem 4:
 Norepinephrine is a neurotransmitter that nerve cells use to communicate. Norepinephrine has been found to be deficient in the brains of Down syndrome mice. Additionally, many children with Down syndrome have a lack of concentration and behavior problems (ADD/ADHD symptoms). According to an article by Dr. Joseph Carver, some studies suggest that children/adults (typical) with ADHD may have only
ten to twenty-five percent of Norepinephrine found in the normal brain.

Related Articles for Problem 4:
Focalin XR
http://www.changingmindsfoundation.org/documents/focalin_xr.html
Stanford – Norepinephrine
http://med.stanford.edu/ism/2009/november/down-syndrome.html
Methylphenidate and Norepinephrine study
http://www.ncbi.nlm.nih.gov/pubmed/20691429
ADHD and Norepinephrine, Dr. Joseph Carver
http://www.enotalone.com/article/4121.html
Remedy for Brain Problem 4:
The benefits realized from adding a mild stimulant medication such as Focalin XR is twofold. First, stimulant medications (ADHD drugs) have been shown to enhance attention and learning. Second, ADHD drugs work on the Norepinephrine system! This type of medication is very individualized. Focalin XR works well for many people with Down syndrome. However, some individuals may have better results using a different stimulant medication.
Thoughts From Teresa Cody
“Do we wait until every detail is known? Did you know that no one knew how aspirin worked until the early 1990's? The details of biological systems are understood more today than any time before but why not use the information in real time? All of the medications in the protocol have been through clinical trials. OK, not specifically for Down syndrome but NO medication has been through clinical trials specifically for Down syndrome. For example, have you ever given your child an antibiotic? We know their immune system can be described at least, as different, if not immunodeficient. But faced with pneumonia or strep throat, the logical decision is to treat with a medication the rest of the population uses. Scientific research has shown that these medications should help correct specific problems in the brain. Problems current science indicates are present in the brains of people with Down syndrome. Some protocol participants have been using the protocol for four years now. The clinical observation of the 300 children and adults on the CMF protocol is that there is an amazing improvement of function including: verbal abilities, long term memory, working memory, gross motor and fine motor. What part of this do you not want?”
Frequently Asked Questions
1.) Is the CMF protocol the solution to all brain problems associated with Down syndrome? No – but it is a start. It is something we can do now to improve cognition as demonstrated by current protocol users.
2.) Will the CMF protocol make my child learn as well as a typically developing child? No – but it does allow most participants to learn and comprehend better than before - now.
3.) Where can I find suggested dosing information? You can find a Dose Chart at http://www.changingmindsfoundation.org/documents/dose_chart.html
4.) How much does the CMF protocol cost? Ginkgo Biloba is widely available, over the counter. It is a standardized formula, so the quality is consistent from brand to brand. A quick internet search found a bottle of GB with 100 capsules for $12.99 from one company. Prozac, generic name Fluoxetine, is available by prescription only. You can get a 30 day supply at most pharmacies for about $4. The cost of prescription ADHD drugs vary – generic drugs are cheaper than name brand. The recommended Body Bio Oils are the
expensive part of the protocol: Phosphatidyl Choline – 100 softgels $62 or a 8 ounce bottle $94, Body Bio Balance Oil (Omega 3,6,9) – 180 softgels $30, 16 ounce bottle $26. Other brands of Phosphatidyl Choline and Sunflower/Flaxseed oils are widely available online and in health food stores.
5.) How do I find more information about starting the protocol? Read the links attached to this paper. They include a wealth of information and will answer many of your questions. You can also order the documentary film and see participants as they are followed while on the protocol (available at  http://www.changingmindsfoundation.org/ ).
6.) How long does the protocol work? Do the kids plateau after being on it for a period of time? According to the CMF, the kids who have been on the protocol the longest are still advancing and learning new things all the time. Just like any medicine, the dosage of these medications have to be rebalanced with time and growth. Be sure to click on “Success Stories” on the CMF's web page for further information.
7.) How do I present this information to my doctor? You can take a copy of this article along with printed copies of the referenced articles linked throughout. Organize the information in a folder and leave it for your doctor to review. Schedule a follow up appointment to discuss after he/she has had time to read the information.
8.) More questions? Contact the Changing Minds Foundation at
changingmindsfoundation@gmail.com

Research Needs Funding –

You Can Help – NOW

We, as individuals, must take it upon ourselves to financially support cognitive research like that being done by Dr. Craig Garner at Stanford's Down Syndrome Research Center. If families do not find cognitive research in Down syndrome a worthy charitable cause, then who else will?
The Changing Minds Foundation currently has two opportunities for you to help fund research to improve cognition in people with Down syndrome. The first is a campaign called,
“Spare Change for Changing Minds.” You can read more about it and learn how to receive your cans for spare change on CMF's home page – click on 'We Can'
The second opportunity is to enter CMF's Ball Drop Contest. Purchase as many numbered golf balls as you want for $25 each. Every ball will give you a chance at a trip to Cabo San Lucas, Mexico!! On October 28th, at Wildcat Golf Club in Houston, all balls will be dropped from a helicopter hovering over the driving range. The first ball to land in the hole (or closest to the pin) wins the trip. The ball drop is limited to 2000 balls. Go to Golf Tournament and Ball Drop
Ask friends and family to support cognitive research by purchasing golf balls.
For Additional Information Please See the Following Websites
Changing Minds Foundation http://www.changingmindsfoundation.org/
Changing Minds Foundation's blog by Teresa Cody
http://www.changingmindsaboutdownsyndrome.blogspot.com/
Join Changing Minds Foundation on Facebook
http://www.facebook.com/pages/Changing-Minds-Foundation-Treatment-and-Research-for-Down-syndrome/101325513376?ref=ts
Join Changing Minds Foundation's NING site where parents discuss the protocol and their children
http://changingmindsfoundation.ning.com/main/authorization/signUp
Stanford's Down Syndrome Research Center
 http://garnerlab.stanford.edu/
http://dsresearch.stanford.edu/research/
Join Stanford Down Syndrome Research on Facebook – keep updated with their blog
http://www.facebook.com/pages/Stanford-Down-Syndrome-Research-Center/378357949509?ref=ts

Cure Down Syndrome? (Part 1)

This essay was written by a mother with a young child with Down syndrome. She did such a terrific job I asked her if I could post it on my blog.  Enjoy!

Cure Down Syndrome?

By Christy Sanchez

According to Webster's Online Dictionary, the definition of cure is to remedy; to remove; to heal. We have always been told that there is no “cure” for Down syndrome. That is – we’ve been told there is no remedy for Down syndrome. But is that really true? Is that really the case in 2010? According to the National Down Syndrome Society, in 1983, the average life expectancy of a person with Down syndrome was just 25 years old. Fast forward to now - the current life expectancy averages 56 years. What caused this change in life expectancy?
Did Down syndrome change in 27 years? Did the trisomy of chromosome 21 change between 1983 and 2010? Of course not - the genetics are exactly the same now as they
were then. A baby born in 2010 with Down syndrome has the same trisomy of chromosome 21 as the baby born in 1983. So what caused the increase in life expectancy? The answer is quite simple – advances in medicine. Not one parent or professional will argue this point. It is evident in the result – longer life expectancy.
Longer life expectancy is now achieved by addressing the physical problems associated with Down syndrome one by one. By identifying the issues that are more common in children with Down syndrome and screening patients – appropriate treatments are prescribed. These common problems have a remedy or cure. For example, an underactive thyroid has a remedy – medication. Celiac disease has a remedy – follow a gluten-free diet. Heart problems such as ASD and VSD have surgical remedies to treat them. People with Down syndrome still have the same triplicated chromosome 21, but there are now remedies for the physical problems associated with the overall syndrome. What do we know about what's different in their brains? Is there a remedy that can help now?
In the last 10 years an accurate mouse model (of Down syndrome), Ts65Dn, has been
developed. According to the NIH National Human Genome Research Institute, the Ts65Dn mouse mimics trisomy 21 (or Down syndrome) and exhibits many of the behavioral, learning, and physiological defects associated with the Down syndrome in humans, including mental deficits, small size, obesity, hydrocephalus and thymic defects. This model represents the latest and best improvement of Down syndrome models to facilitate research into the human condition. In the lab, researchers are now able to reveal answers or remedies for the neurological disorders associated with Down syndrome. Too often when we talk about a remedy or cure for problems in the brains of people with Down syndrome, parents and professionals alike say, “No, a cure is impossible. People with Down syndrome are the way they are – just accept it and move on!” Before you jump to that same conclusion, I encourage you to take a look at current science. Read it yourself. That is exactly what Teresa Cody did. Teresa is the mother of Neal, who has Down syndrome. At the age of 8, Neal couldn't read, write or distinguish shapes. “The main problem was he really couldn't remember. He did not ask questions. He could not verbalize,” said Teresa. “He used to pick up the pen and stare at the paper and you could see he had no idea which way to make the pen go to copy something.” Teresa studied the research. Based on Dr. Craig Garner's work at Stanford, she devised a protocol that contained compounds shown in Garner's research to target the underlying cause of learning and memory problems. Just one year later, Neal was reading at a second grade level and doing multiplication by hand. Neal's academic gains while taking the treatment protocol inspired Teresa to create the Changing Minds Foundation, a 501(c)3 non-profit organization, dedicated to improving the mental ability of persons with Down syndrome – now – with available medical treatments and proper education. A documentary film called 'Changing A Mind' tracked the progress of Neal and several other pilot protocol participants over the course of two years. You can view a trailer of the documentary on their website http://www.changingmindsfoundation.org/

ADHA, ADD, NE, Letters, letters and more letters

Last November there were headlines that read, "A Fix for Down Syndrome Brains" and " Norepinephrine Boosts Memory in Down Syndrome Mouse Mode" and "Norepinephrine could Reverse Down syndrome".

This was and is fantastic. Looking at the study out of Stanford University, Salahi et al. found that increasing the neurotransmitter, norepinephrine (NE), increased contextual learning. They gave the DS mouse a drug called L-DOPS, which increases norepinephrine and epinephrine. This drug is used in kidney dialysis patients for hypotension. So, it increases blood pressure. What an interesting choice. One would not readily use that drug in children or adults with Down syndrome.

But there are a whole group of drugs that one would use in children and adults. They have been used for 50 years in thousands of children, and they also increase Norepinephrine. What kind of drugs could these be?

ADD/ADHD medications!

Ritalin was introduced in 1960. It was not known at that time how the drug worked, but it is now. It increases the levels of Norepinephrine! According to the Stanford study published November 2009, the Down syndrome mouse model benefitted from increased NE. So, maybe all children and adults with DS would benefit from ADHD meds? Not that they are all diagnosed ADD/ADHD, but this may be the next layer of the brain 'onion'.

F.Y.I. --- Other well known ADD/ADHD drugs are Concerta, Vivance, Focalin XR, Metadate, and Desoxyn

Brain Rules - The Numbers Shall Set You Free

I was reading a book called Brain Rules by John Medina and came across some very interesting information. (BTW, I would recommend the book). It seems that babies are born with the same number of neurons and connections as adults have. And then, by the time they are 3 years old, the connections (and therefore number of neurons) have doubled or even tripled. But that doesn't last long. The brain as he puts it 'takes thousands of tiny pruning shears and trims back a lot of this hard work.'
What is remarkable is that at puberty the whole process starts over again. So, the brain explodes with neuron growth and then with vigorously trims it back again. So there is a lot of brain growth and pruning during the terrible twos and then again the the terrible teens.

"Though that might seem like cellular soldiers obeying growth commands in lockstep formation, nothing approaching military precision is observed in the messy world of brain development. ...Even a cursory inspection of the data reveals remarkable variation in growth patterns from one person to the next."

As I was reading this, I was thinking about all the stories of DS kids that decline after puberty. What if DS never get (or get much less) of that explosive neuron growth but have close to normal pruning? This would cause the neuron count to dip below that critical number that keeps coming up.
Elizabeth Goulds work showed that below a certain neuron count, the study subjects get anxiety, and depression. And the brain goes into a 'safe mode' and doesn't initiate the normal neurogenesis that should be happening. The brain some how panics and just tries to hold onto what it has.
Numbers.....could it be a numbers game?