|Down Syndrome with Growth Failure Division|
Linda Blevins, Division Director
Down Syndrome and Growth Failure Division Summer Newsletter
|Reprinted with the permission of The MAGIC Foundation|
1327 N. Harlem Avenue, Oak Park, IL 60302-1376
1 (800) 3 MAGIC 3
(708) 383-0808 Fax: (708) 383-0899
PLEASE SEND ME YOUR STORIES AND PICTURES
Convention is coming. I would like to assemble a photo album of our children. Please send me a photo. If it is difficult to part with a photo, an option to consider is color Xeroxing. These replications are very clear. Help me out and send them soon. Also, I still need your personal stories. It can be a short paragraph to comment on your child's response to GH or it can be a saga, or it can be about a therapy that has worked for your child. I can't wait to start getting those pictures and stories.
Welcome to our new members. Your membership and support is very much appreciated. Continue to share the MAGIC newsletter with other DS parents, professionals, DS groups, therapists, doctors and friends. Remember you can make a difference. Let us share information about the many options of treatment for DS.
ANTIOXIDANT THERAPIES FOR DOWN SYNDROME
What are "free radicals" and "antioxidants"?
They have become buzzwords in our society. Most importantly how do they relate to our Down syndrome children?
The human body is a continuous chain of metabolic reactions. A common spin off of these metabolic processes are molecules called free radicals. Free radicals are charged molecules, which have unbalanced electrons. These free radicals are highly reactive and try desperately to balance themselves. Uncontrolled, free radicals rip electrons from neighboring cells damaging proteins, disrupting DNA and RNA, inactivating enzymes and oxidizing the easiest target of all, fatty tissues in the brain.
Fortunately, the body has internal systems, the antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione (GSH). These enzymes serve a protective role and "scavenge" free radicals. Nutritionally, vitamins such a vitamin A, E, C and minerals zinc and selenium provide free radical protection by trapping these charged molecules and reducing the damage to our bodies.
Are there examples of free radical damage in every day life?
If you slice an apple and leave it sitting on the counter, it will soon turn brown. This is an example of oxidation by free radicals. Now, slice another apple and then dip it in lemon juice or lemon water. The apple will remain white. The vitamin C and the bioflavonoids from the lemon "protect" the apple from oxidation.
If your backyard grill is like ours, it is slowly rusting away. Rusting is another graphic example of the oxidative, free radical process.
How does this relate to down syndrome?
In DS the gene for the enzyme SOD is located on the 21st Chromosome (1,2,3,4), leading to a genetic overexpression of this enzyme. "With over production of SOD, catalase and glutathione peroxidase are challenged to keep up with the accelerated production of hydrogen peroxide. When they don't, excess hydrogen peroxide accumulates in the cells and tissues causing increased oxidative stress, free radical proliferation and accelerated aging" (8).
What do the scientific studies say about DS and SOD?
The SOD genetic overexpression is an area that has solicited much attention. Studies have revealed 50% elevation of SOD levels in the brain and in a variety of blood cells. Italian findings revealed "It has been emphasized that an increased oxidative damage can exist in Down syndrome, and that superoxide dismutase (SOD) seems to play a role in the pathogenesis of this disorder" (3). Another study out of Israel says that this over production of SOD causes increased production of hydroxyl radicals (HO). The study states:
"The most reactive and noxious species is the hydroxyl radical. Its reactivity is so great that when it is formed in living systems, it will react immediately with whatever biological molecule is in its vicinity. One of the major targets is the polyunsaturated fatty acids of membrane phospholipid."(2).Researchers in the United States have come to the same conclusion. Mary Coleman, M.D., of the Children Brain Research Clinic, published "SOD... has been the most studied of the chromosome 21 genes. Research suggest that high levels of this enzyme could effect membrane fluidity and impair membrane function. ... normal brain function is highly dependent upon membrane interactions, particularly at the synapse."(4).
Dr. Capone at the Down Syndrome Clinic at the Kennedy-Kreiger Center in Baltimore writes, "Elevations in SOD activity and increased lipoperoxidation are observed in Down syndrome brain as early as 15-20 weeks gestation. Alterations in the antioxidant defense system have been hypothesized to play a role in AD pathology observed in older persons with DS." "The manifestations of elevated SOD activity and therapeutic strategies to counter this effect will continue to be an important area of research".
Does oxidative stress effect I.Q. levels in DS?
There is a very interesting study that was conducted by Jérôme Lejeune. Lejeune is considered the father of modern genetics and the discoverer of the extra chromosome in DS and Fragile X syndrome. Lejeune was the first to discover amino acid imbalances in DS.
This particular study found:
"A highly positive correlation exists between erythrocyte glutathione peroxidase and I.Q."Translated, this means the more glutathione the individual has, the more efficiently they can deal with the onslaught of the highly destructive free radicals and protect precious brain cells. The study further states:
"Many features of Trisomy 21 are consistent with increased oxidative damages: 1) rapid aging with decreasing intelligence quotient (I.Q.) 2) histological changes in brain similar to that seen in neuronal degeneration with accumulation of lipofuscin such as observed in Alzheimer disease, and 3) shortened life span of cells in culture".Is there a way to test antioxidant vitamins?
|Vitamin A||Vitamin E||Beta-carotene|
|1st quitile||< 1.67 um||< 23.1 um||< 0.2 um|
"In addition, 16/65 (25%) were SIMULTANEOUSLY in the lower quintile for vitamin A, vitamin E and beta-carotene. Random expectation would predict 0.5 individuals. Clearly these micronutrients are being affected as a group" (10). To more clearly state this, preliminary results show that 62 out of 65 DS subjects tested low for vitamin A, 53 out of 65 tested low for vitamin E and 41 out of 65 tested low for beta carotene.
Dr. Thomas states "There can be no question that Down syndrome individuals are under unusual oxidative stress and prematurely display a variety of degenerative diseases" (9).
What are the effects of antioxidant supplementation?
Recently published are the results of a very important study that was conducted at Harvard University. The researchers took fetal DS and age matched normal brain cells and cultured them in the laboratory. They report that "DS neurons subsequently degenerate and undergo apoptosis whereas normal neurons remain viable. Degeneration of DS neurons is prevented by treatment with free radical scavengers or catalase. Furthermore, DS neurons exhibit a three to fourfold increase in intracellular reactive oxygen species (ROS) and elevated levels of lipid peroxidation that precede neuronal death." (7). (Reactive oxygen species (ROS) is another way to say free radicals).
The researchers found that both normal and DS cultures were very similar in the first 5 to 7 days. "From 7 to 14 days in culture, extensive loss of neurons and neurite processes occurred in DS but not in normal control cultures. After 14 days in culture, neuronal viability in DS cultures was markedly reduced to 41% of the value at 7 days whereas neuronal viability in normal cultures did not decline." (7).
The researchers then took another round of neurons and treated them with a variety of antioxidant vitamins and enzymes (vitamin E, N-acetyl-cysteine (NAC), catalase, S-PBN). The treated DS cultures retained 80% to 95% of their viability. The researchers, Buscigilo and Yanker, clearly, scientifically, and medically prove that "antioxidants inhibit the degeneration of DS neurons" (7).
This study is a powerful statement for using targeted nutritional supplementation to manage the gene dosage effect of SOD.As one looks at Dr Wisniewski's startling research that "the brain shape in DS newborns was the same as in non-DS, but after 3-5 months of age in DS the antero-posterior diameter was found to be shorter than in non-DS (11)". Severe oxidative stress may be the major cause of these dramatic brain alterations and a leading cause of the pathology of DS.
WHERE CAN I HAVE MY CHILD TESTED?
Several laboratories that have expertise in testing antioxidant status and some of them have a track record in working with DS.
4622 Santa Fe St.
San Diego, CA 92109
|test antioxidant status and amino acid profiles.|
5000 Peachtree Ind. Blvd.
Norcross, GA 30071
|test antioxidant, amino acids, organic acids, fatty acids, serum chemistries, nutrient minerals.|
1414 Key Hwy.
Baltimore, MD 21230
|test antioxidant status, hormonal biomarkers of growth hormone, DHEA, melatonin, estrogen, testosterone.|
WHAT ANTIOXIDANT INTERVENTION IS AVAILABLE?
Two companies offer vitamins that are formulated for Down syndrome. These companies utilized the most current medical literature and research in compounding their vitamins.
1303 Richmond Rd.
|Vitamins for DS (MSBPlus) and ADD, customized vitamins and specialty compounds.|
HOW DO I GET STARTED?
For every family this is a personal decision. As with all things in life, there are no absolute guarantees and no magical silver bullets offering a "cure". But this is a fact, that DS individuals have medically and scientifically documented metabolic disturbances. The real questions and controversy arises in "What are reasonable testing procedures and what are reasonable therapeutic strategies to manage these metabolic disturbances?"
Education is always a good first step towards making informed decisions. Each of the organizations will be happy to supply information. Metabolic and endocrine test results can give you a window into your child's metabolism and consideration for possible treatment options. Networking with other parents can provide personal experience and useful information. Of course you should always include your physician in this process.
I have a new book. (Don't I always have a new book.) This one is called Growth Hormone by Harvey Scanes and Daughaday, published by CRC Press, 1995. While reading this book one comes to realize how important growth hormone is to our metabolic processes and how a deficiency can have such a profound effect. The book has many highly technical portions. (For some reason I no longer find Danielle Steel novels very challenging reading material).
So many of the symptoms and pathologies discussed in the book would be identical to symptoms and pathologies seen in DS.
SMART DRUG NEWS
CERI (Cognitive Enhancement Research Institute) has been following the evolving research and targeted nutritional therapy for individuals with DS. The April issue has an outstanding article, "Antioxidant Intervention in Down's Syndrome". I recommend every one order a copy at (415) 321-2374. The article presents a persuasive review of the metabolic disturbances and how new testing technologies are helpful in assessing antioxidant status and guiding nutritional intervention strategies.
DID YOU KNOW THAT....
Did you know that one of the key people who help start the National Down Syndrome Congress was a fellow by the name of George Johnson. One of the many original goals of the NDSC was to research Dr. Turkel's vitamin treatment of DS. Mr. Johnson stills runs a newsletter.
George JohnsonFollowing is a chart supporting the use of growth hormone treatment in Down syndrome.
1409 N. First St.
Aberdeen, SD 57401
|DOWN SYNDROME FEATURE||GROWTH HORMONE BENEFITS
|Deficit in head circumference.||"..it is now well established that GH stimulates neuronal and glial proliferation and increases brain and cranial size in young animals" pg. 443.
|Delayed brain development and myelination of cerebral pathways.||"A neurotrophic role for GH is also indicated by the severe deficits in brain development and RNA/DNA synthesis, and impaired proliferation and myelination of neural and glial cell that occur in GH-deficient states." pg. 443
|Slow learning and memory problems.||"GH may influence memory by affecting cholinergic transmission ...or by generally enhancing brain development." pg. 445.
|Decreased height and shortened limbs.||"GH stimulates the cartilage and bone growth by increasing circulating concentrations of IGF-1." pg. 391.
|Hypotonia||"Collagen synthesis is stimulated after only 14 days of GH treatment." pg. 490.
|Low immune response.||"Growth hormone is necessary to maintain lymphatic tissue populated with lymphocytes since the removal of ...GH... results in the atrophy of the thymus gland." pg. 407.
|Abnormal thyroid function.||"GH administration to hGH deficient children is followed by increased circulating concentration of T3 but decreased concentration of T4." pg. 424.
|High amounts of body fat and poor digestion.||"...effects of GH on protein and carbohydrate metabolism.." and "..excess body fat is significantly reduced by GH treatment." pgs 486,485.|
Excerpts from "Growth Hormone" by Harvey, Scanes and Daughaday.
HAVE A SAFE AND FUN SUMMER. HOPE TO SEE YOU AT CONVENTION!!!
|This newsletter has been provided as a courtesy of The MAGIC Foundation. It is for informational purposes only. The MAGIC Foundation does not assume any liability for its content. Consult your physician for diagnosis and treatment.|
|Revised: May 27, 1999.|