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Vaccine Safety Conference: Evaluating the Science January 3-9 2010 Tryall Club West Indies Jamaica

Vaccine Safety Conference: Evaluating the Science January 3-9 2010 Tryall Club West Indies Jamaica
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Aluminum as a neurotoxin: the evidence from cell culture, in vivo, and human studies

Consumer Summary | by Christopher Shaw

Aluminum as a neurotoxin: the evidence from cell culture, in vivo, and human studies

Most age-related neurological disorders appear to arise due to environmental toxins acting against still unknown genetic susceptibility factors (Shaw and Hoglinger, 2008). Determining which of the immense numbers of potential toxins and genes might be responsible is a daunting task but one made potentially manageable by the study of unique disease clusters. For Lou Gehrig's disease (ALS) there are two such clusters. The first was identified on the Western Pacific island of Guam in the late 1940s by American neuroepidemiologists (see Kurland, 1988, for references). The second is the ALS cohort within the multisystem disorder termed Gulf War Syndrome (see Petrik et al., 2007, for references). For both, a range of potential toxins have been proposed. On Guam, epidemiological analysis pointed to consumption of the seeds of the cycad palm (Whiting, 1963, 1964). In vivo studies in male outbred mice fed washed cycad seeds as part of diet showed a range of behavioural abnormalities and neuronal cell losses in different regions of the central nervous system (Wilson et al., 2002, 2004; Shaw and Wilson, 2003; Cruz-Aguado and Shaw, 2009). The range of outcomes resembled the spectrum of the disease on Guam (Shaw and Hoglinger, 2008). Aluminum in the soil had also been postulated to be related to the disease and aluminum neurotoxicity in various circumstances has been well documented (see Tomljenovic and Shaw for references). In neuronal and other cell culture preparations, aluminum salts such as the hydroxide as well as aluminum chloride cause the loss of cells (Zweigers et al., in preparation). Mice exposed to aluminum chloride in water showed a range of motor and cognitive behavioural deficits (Bannon et al., in preparation). Mice injected with the adjuvant aluminum hydroxide showed motor behaviour deficits and motor neuron loss in motor cortex and lumbar spinal cord and a range of cognitive disorders (Petrik et al., 2007; Shaw and Petrik, 2009). Morin staining for aluminum showed that motor neurons in the aluminum treatment group were labeled. Motor neurons also showed the presence of abnormally phosphorylated tau protein, the latter a hall mark of Alzherimer's disease and ALS-PDC (Shaw and Petrik, 2009). In addition to inducing outcomes similar to age-related neurological disorders, aluminum may contribute to early developmental disorders in humans. A comparison of autism spectrum disorder incidence since the early 1990s and the aluminum content in the Center for Disease Control and Prevention's recommended vaccine schedule shows a high level of correlation (Tomljenovic and Shaw, submitted). Overall, the data presented suggest that substances such as aluminum can be highly neurotoxic at different stages of life. Presumptions of vaccine safety for aluminum or other adjuvants based on incomplete data (see GlaskoSmithKlein data sheets) should be reevaluated by adequately powered, controlled, and longitudinal studies involving multiple time points and animals of both sexes.

 

Slide Summary | by Christopher Shaw

Slide 1: Title

Slide 2: Topics to address

Slide 3: Distinguishing causative vs. non-causative events in neurological disease

Slide 4:  Hypothetical timelines of neurological disease progression and where to successfully intervene

Slide 5: Venn diagram of the interactions of toxins, genes, and age

Slide 6: Neurological disease clusters, what they are and aren’t

Slide 7: Changing ASD prevalence (from Tomljenovic and Shaw, 2011)

Slide 8: History and facts about ALS-PDC on Guam (Kurland, 1988; Whiting, 1963, 1964)

Slide 9: Ibid

Slide 10: Some of the toxins found in cycad seeds

Slide 11: The experimental design (Wilson et al., 2002)

Slide 12: Behavioural outcomes from cycad feeding in CD 1 adult male mice (Wilson et al., 2002)

Slide 13: MRI/MRM data (Wilson et al., 2005)

Slide 14: Ibid

Slide 15: Ibid

Slide 16: Compiled data (Wilson et al., 2002, 2005, and others)

Slide 17: Ibid

Slide 18: Ibid

Slide 19: Summary of ALS-PDC to neuronal outcomes in mice fed cycad

Slide 20: Alice down the rabbit hole: introduction to our work on vaccine adjuvants

Slide 21: HIN1 data sheet cover page (GlaskoSmithKline)

Slide 22: Findings from above re animal testing

Slide 23: Some typical vaccines with aluminum adjuvants (from Tomljenovic and Shaw, 2011)

Slide 24: “Pervasive uncertainty”: history of vaccine adjuvants and reference for this term (Glenny et al., 1926; conference report, 2002)

Slide 25: Preliminary data on NSC-34 cells exposed to aluminum hydroxide (Zwiegers and Shaw, in preparation)

Slide 26: IMR-32 cells exposed to aluminum chloride (ibid)

Slide 27: In vivo behavioural data from mice injected with aluminum hydroxide (Petrik et al. 2007)

Slide 28: Labeled motor neurons in control and aluminum-injected mice and graph showing quantification (Petrik et al., 2007)

Slide 29: Motor neurons in treated mice undergoing programmed cell death. Ibid

Slide 30: GFAP labeling for reactive astrocyes in treated mice; Morin staining for aluminum in treated mice. Ibid.

Slide 31: Microglial activation in aluminum injected mice (Shaw and Petrik, 2009)

Slide 32: Labeling of neurons in human cortex (control and AD) and in aluminum injected and control mice (ibid)

Slide 33: Changes in motor behaviours in treated mice (Shaw and Petrik, 2009)

Slide 34: Ibid

Slide 35: Ibid

Slide 36: Cognitive changes. Ibid

Slide 37: Motor and other behavioural changes following aluminum treatment in water of CD1 mice (Bannon and Shaw, in preparation)

Slide 38: ASD incidence graph (from Tomljenovic and Shaw, 2011)

Slide 39: Relation of ASD to aluminum body burden (ibid)

Slide 40: Conclusions and future directions

Slide 41: Acknowledgements and funding support

Slide 42: More acknowledgements

Slide 43: Questions (to audience)

References:

Arepanrix data sheets, GlaskoSmithKline: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/legislation/interimorders-arretesurgence/prodinfo-vaccin-eng.php. See pages 21-22.

Cruz-Aguado R and Shaw CA. The ALS/PDC syndrome of Guam and the cycad hypothesis. Correspondence. Neurology. 72(5):473-477. (2009).

Kurland LT. Amyotrophic lateral sclerosis and Parkinson's disease complex on Guam linked to an environmental toxin. Trends Neurosci. 11: 51-4 (1988).

Petrik MS, Wong MC, Tabata RC, Garry RF, & Shaw CA. Aluminum adjuvant linked to Gulf War illness induces motor neuron death in mice. J Neuromolecular Medicine 9: 83-100. (2007).

Shaw CA and Petrik MS. Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration. J Inorganic Biochem. 103 (11): 1555-62. (2009).

Shaw CA and Wilson JMB. Analysis of neurological disease in 4 dimensions: Insight from ALS-PDC epidemiology and animal models. Neurosci Biobehav Rev. Oct. 27(6): 493-505. (2003).

Shaw CA & Höglinger GU. Neurodegenerative diseases: neurotoxins as sufficient etiologic agents? J Neuromolecular Medicine. 10(1): 1-9. (2008).

Tomljenovic LT and Shaw CA. Does an elevated body burden from vaccine aluminum adjuvants contribute to the rising prevalence of autism? BMC Pediatrics (Submitted, 2010).

Whiting MG. Toxicity of cycads. Economic Botany. 17: 271-302. (1963).

Whiting, MG, Food Practices in ALS Foci in Japan Marianas + New Guinea, federation Proceedings, 23: 1343 (1964). [Medline]

Wilson JMB, Petrik MS, Grant SC, Blackband SJ, Lai J, and Shaw CA. Quantitative measurement of neurodegeneration in an ALS-PDC model using MR microscopy. Neuroimage 23(1):336-343. (2004).

Wilson JMB, Khabazian I, Wong MC, Seyedalikhani A, Bains JS, Pasqualotto BA, Williams DE, Andersen RJ, Simpson R J, Smith R, Craig UK, Kurland LT, and Shaw CA. Behavioral and neurological correlates of ALS-parkinsonism dementia complex in adult mice fed washed cycad flour. J. Neuromol. Med. 1(3): 207-222. (2002).