By Teresa Conrick
This is a continuing look at a hypothesis, using pertinent pieces of evidence-based research, that connects autism and other neurodegenerative disorders to mercury and also to cancer. Read Part 2 and Part 1. Here is such a study related to mercury and breast cancer:
"Methyl mercury influences growth-related signaling in MCF-7 breast cancer cells" (Pubmed)
"Environmental contaminants have been shown to alter growth-regulating signaling pathways through molecular mechanisms that are mainly unclear. Here we report that within a narrow concentration range (0.5-1 microM) methyl mercury (MeHg) significantly stimulated growth of MCF-7 cells, induced Ca(2+) mobilization, and activated extracellular signal-regulated kinase (1/2) (Erk1/2)."
Here also was a report on research done in 2005 that linked Thimerosal to the glutamate issues of autism and the other diseases we are examining:
Study implicates thimerosal in glutamate dysfunction (ARI Newsletter)
"New research links the mercury-laden vaccine preservative thimerosal to dysregulation of the glutamate system. Glutamate, an excitatory neurotransmitter, is crucial to learning and memory, but when present in excess it can cause widespread neuron damage or death. Glutamate abnormalities are increasingly being implicated as a factor in autism, Fragile X syndrome, and other neurodevelopmental disorders."
Please take a moment to read that entire page as it contain some very interesting information. Note also the story of the boy with an autism diagnosis who improved on cough drops that contain dextromethorphan, a glutamate antagonist, which correlates to the past mention in Part 1 - (HERE)
Journal of Environmental Health, 2010 Antagonism of Dextromethorphan and Riluzole to Neurotoxicity Induced by Methylmercury in Rats. I am not endorsing dextromethorphan or any of the medications mentioned here but pointing out the connection from mercury neurotoxin blockers to an increased pharmaceutical cornucopia of using them as medications directed at neurodegenerative diseases, autism and cancer. There is an irony here that cannot be denied and needs to be examined more closely.
It appears that six years ago, when this ARI newsletter was published, there was a connection to glutamate dysfunction in autism but not yet its connection to ALS, Parkinson's, Alzheimer's, Schizophrenia or cancer. Somewhere, it must have become more obvious, which makes it all the more curious as to why Dr. Gorski would not mention that in his blogs, instead of sarcastic hurls targeted towards so many parents looking for answers about their child's regression into an autism diagnosis.
Here is a good synopsis of where we are in Part 3: the pattern - the hypothesis : toxic exposure (mercury) > glutamate dysfunction > altered protein tyrosine kinase - phosphorylation > regression into disease. The following is research showing how each of the diseases has a common denominator of altered or aberrant protein tyrosine kinases and protein tyrosine phosphorylation:
Protein tyrosine kinases in human breast cancer: kinetic properties and evidence for the presence of two forms of native enzyme (NIH PubMed)
Protein tyrosine kinases in malignant melanoma. (NIH PubMed)
Altered protein tyrosine phosphorylation in Alzheimer's disease. (NIH PubMed)
Mitogen-activated protein kinases (MAPK) in schizophrenia (NIH PubMed) (need to add this study for good visual connection : "Role of reactive oxygen species, mitogen-activated protein kinases and signaling cascade in mercury immunotoxicity" (UGA.edu) "This study indicates that mercury suppresses NO synthesis by inhibition of the nuclear factor .B pathway and modulates cytokine expression by p38 mitogen-activated protein kinase (MAPK) activation"
Protein tyrosine kinase activity in T lymphocytes from patients with systemic lupus erythematosus. (NIH PubMed)
Aberrant protein kinases and phosphoproteins in amyotrophic lateral sclerosis (HERE)
Inhibition of protein tyrosine/mitogen-activated protein kinase phosphatase activity is associated with D2 dopamine receptor supersensitivity in a rat model of Parkinson's disease. (NIH PubMed)
"Brain Region-Specific Decrease In the Activity of Protein Kinase C, and Increase In Activated MAP ( mitogen-activated protein) Kinases In Regressive Autism" (IMFAR)
As these connections become more clear, one does not have to look far to see how medications shown to "attenuate MeHg-mediated cell death by blocking NMDARs" would then be coming to your local Walgreens for diseases on the rise:
Riluzole Clinical Trials
"Review of the use of the glutamate antagonist riluzole in psychiatric disorders and a description of recent use in childhood obsessive-compulsive disorder.
Open-label riluzole in fragile X syndrome.
Efficacy of Riluzole in Hereditary Cerebellar Ataxia
Efficacy and Tolerability of Riluzole and Biomarker of Treatment Response in Treatment-Resistant Depression
Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma
Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder
Riluzole to Treat Depression in Bipolar Disorder
Riluzole and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases
A Magnetic Resonance Spectroscopic Examination of Children and Adolescents Taking Riluzole for Obsessive-Compulsive Disorder
Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
Riluzole in Women With Stage I, Stage II, or Stage IIIA Breast Cancer
Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
Double-Blind Placebo-Controlled Trial of Riluzole in Pediatric Bipolar Disorder
Treatment of Refractory Schizophrenia With Riluzole
Memantine or Riluzole Prophylaxis for Corticosteroid-Induced Mood and Declarative Memory Changes
Rapid Antidepressant Effects of Ketamine in Major Depression"
"Riluzole to Treat Childhood Obsessive-Compulsive Disorder and Autism" (NIMH)
In looking at that list, the one study that seems odd and to not fit based on all that has been connected, is the "Efficacy of Riluzole in Hereditary Cerebellar Ataxia." The word "hereditary" is strange in that none of these others include it. In looking at cerebellar ataxia, there appears to be another type:
Cerebellar ataxia presumed due to live, attenuated measles virus vaccine. 1967 (JAMA)
Gait disturbance interpreted as cerebellar ataxia after MMR vaccination at 15 months of age: a follow-up study 2000 NIH PubMed
"Gait disturbance registered after MMR vaccination seems to be more frequent than hitherto reported."
Is it possible that viruses can also be involved in this process?
Effect of persistent measles virus infection on protein kinase C activity and c-fos protooncogene expression in neuroblastoma cells 1989 (NIH PubmMed )
Reversal of the measles virus-mediated increase of phosphorylating activity in persistently infected mouse neuroblastoma cells by anti-measles virus antibodies
(VIRSGMJournals) 1994 "These results demonstrate that measles virus induces elevation in cellular phosphorylation which is essential for measles virus production."
Since many children had developmental-medical regression after vaccination, and a majority with thimerosal-containing vaccines, coupled with often another regression with significant health issues after the combined MMR vaccine, is it possible that these connections and this hypothesis shows a mechanism to illness and disease? These authors seem to follow this idea:
"Mercury is widely distributed in the biosphere, and its toxic effects have been associated with human death and several ailments that include cardiovascular diseases, anemia, kidney and liver damage, developmental abnormalities, neurobehavioral disorders, autoimmune diseases, and cancers........several genes that encode for proteins in the intracellular
signaling cascades that are activated by receptor tyrosines were initially isolated as oncogenes in cancer cells or tumor viruses [21, 25, 58, 59]. This finding implies that the origins of most diseases are linked via exposures to chemical and other environmental xenobiotics including mercury. Degree of toxicity depends on mercury species, dosage, individuality and the type of MHC association [10, 43-48]." 2006 International Journal of Environmental Research and Public Health (HERE)
In Part 4, we will go back in time to one of the original Kanner patients.
Teresa Conrick is Contributing Editor for Age of Autism.