This article was first published in the Down's Syndrome Association Newsletter July 1997. For reprints please contact that organization in London, England. Telephone no. +44 (0)20 8682 4001 or FAX no. +44 (0)20 8682 4012 .

My Daughter Ellie was born in November 1996. She was diagnosed as having Trisomy 21 about a week after her birth.

After recovering from the emotional reaction experienced by all parents of a new baby with Down's, I began to research (as all parents do), in an attempt to understand what I could of the nature of Ellie's "condition".

What appears below is an overview of the outcome of one aspect of my investigations, which from reports of discussions that took place during the recent Under 5's conference, I'm sure will be of interest to all parents of children with Down's, but particularly to new parents.

Although this contribution to the (DSA) "Newsletter" was invited, I should make it clear that the opinions expressed here are my own, and not necessarily those of the DSA, its officers or trustees.

In writing this overview, I have "lifted" text from the work of a number of authors and organisations. In particular I should mention the Cognitive Enhancement Research Institute, Trisomy 21 Inc. and Nutri-Chem.

The History

In 1866 John Langdon Down first describes some of the characteristics in children whose disability now bears his name.

The attempt to "treat" children with D.S. began in the 1930's. Until very recently, much of the scientific community, and particularly the medical profession has been very sceptical of the value of such an approach. The view taken being that Down's after all is a "genetic" condition, and as such, cannot be treated.

In the face of concerted opposition however, people like Dr. Henry Turkel, began to formulate vitamin and mineral supplements in the 1950's, which appeared to have beneficial effects on children with Down's.

In 1959 Dr. Jerome Lejeune discovered that Down's was caused by an extra chromosome, (usually at the 21st set of chromosomes)

The Human Genome Project, which began more than 10 years ago, and is still continuing, has systematically attempted, with some considerable success to map out and identify the bio-chemical functions inherent in gene.

With the benefit of the gene map, it became possible to examine, understand, and attempt to isolate the functions of individual genes.

In 1976, the "switch" controlling the production of a enzyme, superoxide dismutase (SOD1) is localised to chromosome 21.

In 1982, the understanding of the role played by SOD is developed by P. Sinet, and it becomes clear that because they have three chromosomes at the 21st set, people with Down's have three "switches" (one on each chromosome) controlling the production of SOD1, rather than two in a person without Down's. Consequently, it is established that people with Down's produce 50% too much Superoxide Dismutase.

The Theory of Genetic over-expression

Unlike most other genetic conditions which are characterised by a deficiency (deletion) or change (mutation) of the genetic material, Down's is characterised by a duplication of all or part of the 21st chromosome. Normally, each cell in the body is supposed to have two 21st chromosomes (one derived from the mother's egg and the other from the father's sperm). Every time a cell divides, each of the 46 chromosomes must be duplicated and separated, one copy of each chromosome ending up in each daughter cell.

Sometimes the process of pulling apart the duplicated chromosomes malfunctions, and both copies of one of the 21st chromosomes end up in the same daughter cell. In other words, one cell has only one 21st chromosome (which fails to replicate) and the other has three 21st chromosomes. This is why Down syndrome is referred to as Trisomy 21 (tri means three, somy refers to chromosome).This extra genetic material causes over expression of the duplicated genes. In other words, genes make both enzymes and proteins, and too many genes lead to too many enzymes and proteins. This, in turn, distorts the way the body works, altering the normal metabolism, development and growth of the body, in some respects, the metabolic system in people with Down's is unbalanced, and the system is unable to process complex nutrients, protect and repair itself in the way that automatically occurs in the system of a person without Down's.

Superoxide Dismutase (SOD) The key theoretical concept underlying nutritional intervention in Down's syndrome is metabolic correction of this and other genetic over-expressions.

Although the extent of the metabolic disturbances in Trisomy 21 is not fully known, some of the more significant disturbances are now becoming better understood, amongst which is the role played by Superoxide Dismutase SOD.

Superoxide dismutase (SOD) is a vital free-radical scavenger. Its job is to mop up stray superoxide ion radicals (O2-) and convert them to hydrogen peroxide. Hydrogen peroxide is then detoxified by other enzymes (catalase and glutathione peroxidase). Normally, SOD is in balance with catalase and glutathione peroxidase. But in Down's syndrome, there are three copies of the SOD gene instead of the normal two. With overproduction 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.

When endogenous (internally manufactured) antioxidant enzymes (catalase andglutathione peroxidase) are overwhelmed with hydrogen peroxide, exogenous (dietary) antioxidants are forced to take up the slack. This greater-than- normal burden on exogenous antioxidants is evidenced by depleted levels of vitamins A, E and/or C, zinc, selenium, and/or glutathione in untreated Down's syndrome individuals.

Targeted Nutritional Intervention (TNI)

Targeted Nutritional Intervention is a therapy designed primarily, but not exclusively, for children with Down's Syndrome. As set out above, much evidence exists which shows that our children are producing too much of the enzyme superoxide dismutase, the "switch" for which is at Chromosome 21.

Further evidence exists which shows that an excess of SOD leads to the premature oxidisation and death of brain cells, through a mechanism described, for example, in Nature in December 1995. The article in nature, which originated from the Dept. of Neurology at Harvard Medical School, further showed how in vitro, the degeneration of neurons in DS cells was prevented by the application of anti-oxidants.

TNI therapies are aimed at correcting nutritional imbalances in general, and in particular are aimed at attempting to correct the consequences of the over-expression of SOD.

Both major suppliers of TNI's, (Nutri-Chem in Canada who manufacture a supplement called MSB+, and International Nutrition Inc., in the USA who manufacture a supplement called Nutrivene-D), manufacture supplements that contain similar mixtures of vitamins, minerals, amino acids, and digestive enzymes. The latter being necessary to re-balance the digestive system which is known to be in some respects abnormal in people with Down's, preventing the absorption of certain nutrients, particularly B complex vitamins.. These supplements are both specifically designed to act as anti-oxidants, and counter-act the oxidative stress experienced in the systems of people with Down's. MSB+ can be ordered with or without the addition of Piracetam. Nutrivene-D is only available without Piracetam.

Piracetam

Piracetam is an optional constituent of MSB+. Some considerable controversy surrounds the use of Piracetam in children with Down's. Piracetam, is one of the family of so called "smart drugs", which allegedly improve intellectual performance. It is reputed to be an intelligence booster and CNS (central nervous system) stimulant with no known toxicity or addictive properties. It is further reputed that Piracetam protects cells from oxidisation, and enhances "inter-hemispheral connectivity" - in other words it improves the exchange of electrical impulses between both sides of the brain.

The effects and safety of Piracetam are said to be so impressive, that piracetam has prompted the creation of a new pharmaceutical category called nootropics.

The term nootropic comes from the Greek meaning "acting on the mind". Piracetam is said to enhance cognition under conditions of hypoxia (too little oxygen), and is also reputed to enhance memory and some kinds of learning in humans. Outside of the USA, piracetam is used to treat alcoholism, stroke, vertigo, senile dementia, sickle cell anaemia, dyslexia, and numerous other health problems. It is widely used throughout Europe to treat a number of conditions such as Alzheimer's in the elderly, and Attention Deficit Disorder, in children.

It is prescribed in the UK to adults only, and then only for a very limited range of conditions. Despite not being available by prescription for children in the UK., it is perfectly legal to import Piracetam, into the UK, in small quantities for personal use, for instance as a constituent of MSB+.

My experience of TNI

From my (and I suspect any parent of a child with Down's) perspective, the prospect that this sort of nutritional intervention might prevent the premature degeneration of cell tissue, and particularly the degeneration of brain cells in my child was very persuasive, especially when set beside the fact that the overwhelming proportion of people with Down's begin to display Alzheimer's like symptoms of degenerative brain disease by their 40's. this is not surprising, given that the amyloid plaque pre-cursor protein, which is linked to the development of Alzheimer's, has recently been tracked to a gene in the 21st pair of chromosomes.

After much thought, and three solid months research, we started giving Ellie MSB+ (with Piracetam) at the age of four months. This nutritional intervention was combined with other forms of intervention such as portage, and cranial osteopathy.

At the time of writing, Ellie is 17 months old. Apart from being perhaps a little behind in her fine motor skills, in all other respects she seems to be not far from following a virtually "normal" developmental curve.

She has complied with simple requests such as "Ellie give me that" from about 13 months. She has a limited vocabulary - Daddy, no, up. She began to crawl at 14 months, can stand up unaided, and clearly will be walking in the very near future.

Although we have no objective evidence, it is clear to us that this nutritional intervention is helping Ellie.

Medical Research And The Future

Ultimately, having gained a better understanding of the bio-chemistry we should aim to do what is already theoretically and practically possible, and that is to engineer a peptide or group of peptides that act as analogues of the those genes that are the major causal factors of the DS phenotype.

Clearly more research needs to be done. It is truly astonishing that given that Down's is the greatest single cause of intellectual impairment, that so little research has taken place.

There are answers out there that will help our children, and future generations of children with Down's, but they will not be found without research.

As a trustee of the DSA, I'm delighted that the association is sponsoring research into these areas. Of course, medical research is expensive, and the urgent need for fund raising and sponsorship specifically for medical research, will clearly become a priority that will be shared by us all.

For further information concerning targeted nutritional intervention and to obtain supplies of nutritional supplements by mail order contact :-

Nutri-Chem Limited,
1303 Richmond Road, Ottawa, Ontario, Canada K2B 7Y4
Tel: 613-820-4200 Fax: 613-829-2226

UK Contact address:

Nutrichem,
28 St. Thomas' Road, Worthing, West Sussex, BN14 7JW
Phone: 0870 740 7815  Fax: 0870 740 7816

To review the latest information on TNI from this company you can visit their Website at

Their E-mail is Nutri-Chem@aol.com
UK Sales E-mail is uksales@nutrichem.com