Smart Drugs & Down’s Syndrome: Part 2

Antioxidant Intervention
in Down’s Syndrome

by Steven Wm. Fowkes

Two years ago, we published our first article about smart drugs and Down’s syndrome which focused primarily on clinical approaches. This article will begin an extensive discussion of metabolic and biochemical mechanisms underlying Down’s syndrome — and proposed nutritional interventions which may mitigate these metabolic disturbances.

Genetic Overexpression

Unlike most other genetic conditions which are characterized by a deficiency (deletion) or change (mutation) of the genetic material, Down’s syndrome is characterized 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’s syndrome is referred to as trisomy 21 (tri means three, somy refers to chromosome). This extra genetic material causes overexpression 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 normal metabolism and development.

Nutritional Intervention

The key concept underlying nutritional intervention in Down’s syndrome is metabolic correction of genetic overexpression. Although the extent of the metabolic disturbances in trisomy 21 is not fully known, several of the more significant disturbances are now becoming well characterized. Effective metabolic management of these disturbances offers the hope of ameliorating the disability typically associated with untreated Down’s syndrome. The degree of amelioration must depend on 1) the metabolic effectiveness of the intervention, and 2) the age at which it was begun. Early clinical reports by physicians and anecdotal reports by parents utilizing some of the approaches that will be discussed in this article suggest that functional normalization of growth rate and cognitive development is a reasonable expectation if intervention is begun early in life. This possibility is at complete odds with the orthodox view that Down’s syndrome infants are born retarded and that treatment is fundamentally futile.

Several of the major metabolic pathways known to be disturbed in trisomy 21 are directly attributable to genetic overexpression. Perhaps the most important example of this is destabilization of the antioxidant defense system by over-expression of the enzyme superoxide dismutase (SOD), which is located on the 21st chromosome. Overexpression of the enzyme cystathionine beta-synthase seems to be significantly responsible for the metabolic disruption of “active” methylation pathways (the SAM cycle). And connective tissue problems appear to be directly attributable to overexpression of collagen genes on the 21st chromosome. Other metabolic disturbances have not been tied to specific genes. As examples, tryptophan deficiency and ammonia accumulation are common features of Down’s syndrome. Fortunately, these metabolic disturbances are just as amenable to nutritional intervention as those tied to genes. The remainder of this article will be devoted to discussing the antioxidant disturbances associated with overexpression of SOD... (end of online article)

Begin Summary of Remaining Contents...

Section: Superoxide Dismutase: “Superoxide dismutase (SOD) is a vital free-radical scavenger...”

Figure 1: Interactions between SOD, catalase and glutathione peroxidase.

Figure 2: Hydrogen peroxide flow in trisomy 21.

Sidebar: What are free radicals?

Section: Glutathione: “Glutathione (GSH) is a central player in the antioxidant defense system...”

Figure 3: The recycling of glutathione.

Section: Glutathione Peroxidase: “Glutathione peroxidase (GSHpx) is an endogenous antioxidant enzyme that detoxifies hydrogen peroxide...”

Section: The Antioxidant Defense System: “The control of free radicals and oxidizing agents...”

Section: Antioxidant Assessment: “In the last decade, several new testing technologies have been developed...”

Section: Additional Metabolic Issues: “Part 3 of this series will continue in the next issue with a discussion of metabolic disturbances relating to methylation metabolism, collagen synthesis, tryptophan metabolism and ammonia detoxification.”

Section: References: five references are provided.