William J. Walsh, Ph.D., Chief Scientist at HRI-Pfeiffer Treatment Center, is a biochemist with more than 30 years of research experience. Dr. Walsh has worked for some of the most prestigious scientific institutions in the country, including Argonne National Laboratory, where he spent 22 years as a researcher. His research and volunteer work involving biochemical predisposition to behavior disorders led to Dr. Walsh's foundation of the Health Research Institute in 1982 and the Pfeiffer Treatment Center in 1989, as non-profit organizations. HRI-Pfeiffer evaluates and treats biochemical imbalances associated with ADHD, behavior disorders, depression, autism and schizophrenia.

MT Protein and Its Role In Autism

The Pfeiffer Treatment Center (PTC) has discovered that diminished metallothionein protein (MT) activity is a distinctive feature of autism. This abnormality (believed to be genetic) results in impaired brain development and extreme sensitivity to toxic metals and other environmental substances. This disorder is often unnoticed in infancy and early childhood until aggravated by a serious environmental insult.

In a study of 503 autism-spectrum patients, we found abnormal levels of copper and zinc in blood (p<0.0001) indicating a failure of the MT protein system to fulfill its role in regulation of these metals. In humans, MT proteins regulate blood levels of these metals, detoxify mercury and other heavy metals, and assist in neuronal development. The expected consequences of diminished or defective MT functioning during gestation or early childhood are consistent with most of the classic features of autism. We conclude that a compromised MT protein system may represent a primary cause of autism.

There are four general classes of MT protein: MT-I and MT-II are found in cells throughout the body, with MT-III restricted primarily to the brain, and MT-IV to squamous epithelial cells in the upper G.I. tract. MT functioning involves (1) induction of thionein, (2) "pre-loading" with Zn atoms, and (3) redox reactions in which Zn may be displaced by other metals.

Since MT is directly involved in neuronal development and maturation of the brain and G.I. tract, the timing of environmental insults is critically important. Temporary disabling of MT function during a specific stage of brain development (e.g., the speech center) may result in an enduring disability in this area. Multiple insults can result in multiple disabilities. If serious toxic insults are avoided until after age three, the brain and G.I. tract may have sufficiently matured so that autism is no longer possible.

MT proteins have been the subject of intensive research and the mechanisms of formation and utilization are now well understood. This information provides a roadmap for treatment of persons with a compromised MT protein system. After autism onset, MT proteins may be chronically contaminated with excessive amounts of copper, mercury, and other toxic metals which can weaken normal MT activity and have an adverse effect on learning, socialization, behavior control, and immune function.

The Pfeiffer Treatment Center (PTC) has developed a nutrient therapy to promote MT protein activity in the G.I. tract, brain, and elsewhere. This protocol is based on 1,200 published articles describing MT synthesis, activation, and redox mechanisms. A total of 22 nutrients which enhance MT were identified and tested in informal clinical trials involving PTC staff and volunteer autism families.

The scientific literature clearly indicates that most of the body’s MT is induced by zinc, with glutathione (GSH) needed for loading apo-MT with zinc and glutathione disulfide (GSSH) required for redox exchange. Selenium and the GSH/GSSH redox couple enhance (a) delivery of Zn to cells and (b) sequestering of mercury and other heavy metals. The equilibrium constants for binding of MT to heavy metals are remarkably large, with the net result that Zn-MT is a "magnet" for these toxic metals.

MT proteins are composed of 14 amino acids and zinc. Many autism-spectrum patients are unable to efficiently cleave dietary proteins into the individual amino acids needed for MT synthesis. Our formulation includes all 14 amino acids, in the proportion found in MT. The large amounts of cysteine required for MT synthesis can be supplied in the form of oral GSH which breaks down in the G.I. tract with minimal side effects

We found that aggressive zinc loading must precede full-scale MT Promotion therapy for best results. Each molecule of MT requires 7 atoms of zinc (Zn) for proper functioning. If MT is formed too rapidly at the intestinal mucosa, temporary severe zinc depletion in the periphery & brain can occur, resulting in irritability and other side-effects.

Our best clinical outcomes have been achieved using a two-phase protocol: (1) preloading with Zn and augmenting nutrients, followed by (2) cautious, gradual introduction of MT promotion formulations.

The Pfeiffer Treatment Center (PTC) has submitted patent applications for the MT-Promotion formulations to ensure that they will be widely available at low cost. Because of the need for medical supervision, the MT-Promotion formulations are available by prescription only.

Promotion of the MT protein system is expected to provide many benefits to autism-spectrum patients including (1) elimination of toxic metals, (2) protection against future toxic exposures, (3) normalization of the G.I. tract, (4) improved behavior control, (5) improved immune function, (6) and enhanced development of brain neurons and synaptic connections. The first 5 benefits may be attainable in the first year of treatment, regardless of the patient’s age. However, the rate of formation of new synaptic connections declines rapidly with age, and early intervention is critically important for development of speech, cognitive advancement, etc. Great patience is needed in treatment of older children who can be expected to progress at a relatively slow rate. For example it may require years for a 10 year old to achieve the same cognitive progress achieved by a 2 year old in a few weeks. Behavioral therapies which shower the brain with impulses and promote neuronal development are especially recommended in conjunction with MT Promotion therapy.

The extent to which the genetically weakened MT system can be promoted is presently unknown. Adjunct therapies which reduce MT requirements by strengthening the immune system, overcoming yeast overgrowth, metal detoxification, etc., may be very helpful in maximizing MT functioning in the brain.

PTC has been testing a new chemical analysis for direct measurement of MT levels in red blood cells, and has obtained the world’s first direct MT data for autistic-spectrum patients. We believe that this chemical assay will be critically important in determining a patient’s MT status and in monitoring treatment effectiveness. The early work includes (1) development of reference normals and (2) comparison of MT levels in autistic subjects and age/gender matched controls.

We believe that the genetically-weakened MT protein system is a primary cause of autism, and that MT-Promotion therapies may be necessary to enable autistic children to achieve their full potential.