Research We Help Fund

Dr. Anju Iona Usman
Dr. Vijendra Singh
Sydney M. Finegold, M.D.
Andrew Wakefield, FRCS
Dr. Jeffrey Segal
HRI-Pfeiffer Treatment Center
Dr. Jeff Bradstreet
Paul Shattock

View Dr. Usman's recent presentation:

Minerals, Metals Mercury, and Miracles in Autism Spectrum Disorders

Please note that this is a large file (1.7 MBytes), so it make take awhile to download.

Also note that The BHARE Foundation has shortened the presentation by removing some slides of pictures and some lab tests.

Dr. Vijendra Singh, a neuroimmunologist, is working on the developmental aspect of the immune system and nervous system and it’s relationships to autism. He firmly believes that up to 80% (and possibly all) cases of autism are caused by an abnormal immune reaction, commonly known as autoimmunity. Specifically, he is exploring the role of autoimmune factors (for example, viruses, autoantibodies, T cells, cytokines, ect.) because they serve as the prime targets of therapy with immune modulating drugs, he said.

Dr. Singh thinks that autism is a complex disorder of a very complicated interaction between the nervous system and the immune system. He postulated a "Neuroautoimmunity Model of Autism" which he recently discussed at two recent meetings: First, the Biomedical Treatments for Autism and PDD Conference held in Orlando, Florida (May, 1999); and secondly, the Neuro-Immune Dysfunction Syndromes (NIDS) Conference held in Bethesda, Maryland (June, 1999). Briefly, he hypothesized that an autoimmune reaction to brain structures, in particular myelin sheath, plays a critical role in causing neurological impairments of patients with autism. He thinks that an immune damage to developing myelin (after a natural infection or vaccination) causes "nicks" or small changes in the myelin sheath, which ultimately leads to life-long problems of higher mental functions such as the skills for learning, memory, communication, social interaction, etc.

Dr. Singh believes that autoimmunity has a strong prospect for treating patients with autism. He said that the lessons learned from other autoimmune diseases should also apply to autism. Because of autoimmunity involvement, he emphasizes the need to focus on immune therapies and urge doctors to pay attention to this line of research. Consequently, he says, there is a strong potential for restoring brain functions in autistic patients, including children as well as adults. With this goal in mind, Dr. Singh is committed to finding a cause and cure for autism.

View Dr. Singh's recent paper:
Prevalence of serum anitibodies to caudate nucleus in autistic children.

For further information, please contact him directly:
Dr. Vijendra Singh, Ph.D.
Biotechnology Center
Department of Biology
Utah State University
4700 Old Main Hill
Logan, UT 84322-4700
E-mail: singhvk@biology.usu.edu

The following hypothesis, based on the work of Ellen Bolte, is at the heart of the research that is being done at the Wadsworth Anaerobic Bacteriology Laboratory, West Los Angeles, CA. Hypothesis: A bacterial toxin, genetically related to the clostridial neurotoxins, causes the behavioral abnormalities associated with autism (via severe disruption of neurotransmitter release) in a narrowly defined subset of children.

Many autistic children have severe gastrointestinal problems. Chronic diarrhea or loose stools is commonly reported from parents of autistic children. The research team at the Wadsworth Laboratory speculate that broad-spectrum antibiotics (frequently used to treat ear infections) may cause significant disruption of the protective intestinal tract flora and that this disruption may allow for colonization by one or more neurotoxin-producing bacteria. The neurotoxin produced in the intestinal tract then ascends to the central nervous system and creates an on-going state of neurotransmitter disruption.

In an initial study, eleven children were treated with a minimally absorbed oral antibiotic. Nine of the eleven children showed improvement during therapy. One child had no change and the other possibly became worse. Pre-treatment stools were found to have numerous unidentifiable Clostridium species. No Clostridium were found in the stools from the "on-therapy" specimens of the children that benefitted from the treatment. Interestingly, the "on-therapy" stool specimen from the child who appeared to deteriorate during treatment contained multiple Clostridium species. The improvements in these children was short term and did not continue after treatment was terminated. However, the fact that there was improvement in such a short time period, shows that it is highly probable that a bacterial infection causes or worsens at least some (if not all) of the autistic symptoms in these children.

The research team is working to identify the specific offending organism(s) involved, which causes the autistic symptoms. Upon isolation of the organism(s), the team will then be able to determine an effective treatment for the elimination of this "bug" from the gut. This work looks extremely promising. The BHARE Foundation feels it is simply a matter of time before this research yields discoveries that will directly benefit our children.

Sydney M. Finegold, M.D.
Professor of Medicine, Professor of Microbiology & Immunology
Infectious Diseases Section
VA Medical Center West Los Angeles
UCLA School of Medicine

Andrew Wakefield, leads a team of eight medical and scientific researchers, investigating a meta-hypothesis; that a complex relationship between a genetic predisposition, and early environmental exposures results in immune derangement and metabolic dysfunction. This primary sequence of events takes place in the gut which then triggers an autistic disorder.

Andrew Wakefield's particular interest is in children who develop normally and then manifest an autistic disorder combined with gastrointestinal symptoms. A few years ago such cases were very rare. More recently there is evidence of a significant increase in their prevalence. Wakefield and colleagues have dubbed this syndrome 'autistic enterocolitis'. Examples of three current programmes receiving assistance from the BHARE Foundation are mentioned below.

Histopathologist Dr Andrew Anthony, is investigating the gut pathology of autistic enterocolitis, and assessing possible non-invasive tests of specific features of the gut disorder seen in autistic enterocolitis. At present most children referred to Andrew Wakefield's colleagues require ileo-colonoscopy, an invasive procedure for which there is a lengthy wait. Children with autistic enterocolitis display a remarkable uniformity in their endoscopic and histological symptoms. At present 98% of affected children show a distinctive pattern of swollen lymph glands at the end of the small bowel and 88% have inflammation of the large bowel.

Immunologist Dr Paul Ashwood, is investigating specific immunologic features of autistic enterocolitis. These concern the apparent dysregulation of certain helper T cells, thus impairing their ability to stimulate a full cytotoxic response from particular classes of cytolytic T cells. Epidemiologist Dr Scott Montgomery, is engaged in population-based studies to confirm the reported temporal trends in the epidemiology of autism. These studies will be used to explore explanations for the apparent increase in the incidence of autistic spectrum disorders and the reported changes in phenotype, such as an increase in the number of children with regressive autism. The work will include an investigation of the role of potential risk factors for autism, specifically the combination of environmental exposures resulting in disease among susceptible individuals. Identification of markers of susceptibility in both parents and the children themselves will also assist in defining the 'at-risk' group for specific exposures. Other current and planned investigations, include studies in virology, molecular biology, genetics and two trials of potential therapies.

For further information please contact Andrew Wakefield at 01144-1225-329-317 or by e-mail via robertsawyer@aol.com (Robert Sawyer handles all general enquiries and research funding for Andrew Wakefield and his research team).

Andrew Wakefield, FRCS FRCPath
Chief Medical Scientist, Visceral
ICDRC Research Director

Dr. Jeffrey Segal has focused on work that addresses the observation that the number of new cases of autism is rising. Though there is likely a genetic predisposition to the clinical syndrome, various environmental factors (such as toxins or infectious agents) are possible co-conspirators. Dr. Segal's early research is focused on a major detoxification pathway, metallothionein (MT). This protein keeps heavy metals such as mercury from causing harm. Two projects that are currently funded are looking to see whether autistic children have mutations in MT genes and/or whether these cells can make the appropriate amount of MT in response to toxins. This research is particularly relevant given the controversy surrounding vaccines/thimerasol and potential chelation therapies.

Dr Segal is working with Dr. Steve Walker at Wake Forest University School of Medicine in leveraging an exciting new technology- gene chip arrays- to help us pose the right questions. This technology works on the principle that "all bets are off" and it is important to look at the big picture for patterns. Gene chips look at how much mRNA is made for thousands of different genes. mRNA is generated from DNA and is used to make proteins. Different cells make different quantities of mRNA. Pancreatic cells make many copies of mRNA for insulin, while heart cells do not. So, useful information is obtained when they survey cell types that are likely to be "different" than controls. They plan to take blood cells, GI cells, and brain cells (from samples that were removed for reasons unrelated to this study) and see what mRNA levels are like for 3,000 to 8,000 genes relative to controls. Based on these differences they will then generate hypotheses that can be tested.

There are many reasons to exploit this technology. First, it makes no presuppositions regarding theories of autism. It delivers an incredible amount of raw data for minimal expense. (If toxins cause symptoms in children unable to detoxify, they will see differences in the common detoxification pathways. If cytokines related to infections are causing damage, they will see differences in common inflammation pathways.) Second, there are almost certainly different subsets of autism. To illustrate, some children respond well to some nutritional supplements. These same supplements are disastrous for other children. They will measure how children respond to different treatments and record this data as well as the information derived from the gene chip profile. They will catalogue these results. In the future they should be able to predict which treatment will be most likely to work for a particular child. In a sense, they will take a lot of the guesswork out of the treatment. Finally, this technology can be used to quickly measure response to different treatments. Current methodologies look for change in eye contact, differences in language function, and the like. These measures are fuzzy and hard to compare. In addition, some of these changes only occur after many weeks. Gene chip technology should show changes, in responders, much more quickly.

HRI-Pfeiffer Treatment Center has discovered that defective functioning of metallothionein protein (MT) is a distinctive feature of autism spectrum disorders. This abnormality results in impaired brain development and extreme sensitivity to toxic metals and other environmental substances.

In May of 2001, William Walsh, Ph.D. and Anjum Usman, M.D. presented HRI-Pfeiffer’s study, “Disordered Metal Metabolism in a Large Autism Population”, at the American Psychiatric Association’s annual conference in New Orleans. Evaluating the biochemistry of 503 autism-spectrum patients, HRI-Pfeiffer found abnormal levels of copper and zinc indicating defective functioning of MT proteins. The expected consequences of defective MT during gestation or early infancy are consistent with several classic symptoms of autism. It appears that defective functioning of MT proteins may represent a primary cause of autism. This research study, along with continuing research on autism, is incorporated into HRI-Pfeiffer’s individualized nutrient therapies for autism spectrum disordered patients.

HRI-Pfeiffer Treatment Center is a non-profit organization dedicated to research, treatment, and education in the field of biochemistry. HRI-Pfeiffer’s scientists have been researching brain chemistry and its relationship to behavior, thought, mood, and learning for about 25 years. The clinic, located in Warrenville, has been treating patients since 1989. The physicians, nurses, scientists, dietician, and support staff work as a team to correct biochemical imbalances that may cause symptoms of autism spectrum disorders, ADHD, behavior disorders, depression, anxiety, and schizophrenia. Each patient is given an individualized prescription of vitamins, minerals, and other nutraceuticals in an effort to correct their specific biochemical imbalance.

The BHARE Foundation’s donations to HRI-Pfeiffer support clinical research intended to develop advanced MT promotion therapy. Pfeiffer is testing promising therapies aimed at improving MT function. This requires (1) elimination of copper and toxic metal overloads and (2) enhancement of synthesis, loading, and redox exchange processes of MT. To conduct this research, Pfeiffer is carrying out tests of 10 to 20 volunteers to determine the efficiency of copper removal for each of these promising therapies: (1) Pfeiffer MT Promotion Formulation, (2) clatherating agents (forms irreversible bonds with toxins, rendering them benign), and (3) Trientine (chelating agent that pulls copper out of the blood). Before-and-after testing of copper, zinc, and ceruloplasmin, and other laboratory assays will measure the kinetics and effectiveness of each technique. The best therapy will be applied to patients with autism and other clinical populations.

Recently, members of The BHARE Foundation began asking "what if" questions and learned that hormone levels in autistic children have not been studied.

Dr. Walsh at The Pfeiffer Treatment Center was contacted and asked to begin a pilot study on this topic. The BHARE Foundation is now supporting the Pfieffer clinic to conduct this study that will measure certain hormones. If hormone levels are found to be different in the autistic children compared to normal controls, potential therapies will be explored and a "phase 2" trial will take place.

HRI-PFEIFFER TREATMENT CENTER
4575 Weaver Parkway
Warrenville, IL 60555
630-505-0300
info@hriptc.org
www.hriptc.org

Send us an e-mail at bharefoundation@sbcglobal.net