Neurotoxicity & Pathology of T-2 Toxins mimics ALS Pathology
A review of T-2/HT-2 Toxins17 summarized the mounting evidence of its profound neurologic toxicity. The pathology of T-2 toxin mimics the pathology found in ALS. T-2 toxins are able to be absorbed across skin, mucosa and the blood-brain barrier accumulating in the CNS. They induce reactive oxygen species with oxidative stress reactions. They cause mitochondrial dysfunction and damage to a cascade of signaling pathways including p53, MAPK, Akt/mTOR, PKA/CREB and NF-kB with neuronal cell death. They cause perturbations of the mitochondrial respiratory chain with loss of ATP energy supplies. The motor neurons of the spinal cord have a relatively high demand for ATP.
Immune Suppression due to Mycotoxins :
Many mycotoxins cause damage to the immune system. The immunotoxicity of trichothecenes may be their most significant pathologic effect and T-2 toxin represents the most toxic of the trichothecenes. Li, M. et al in 200622 found T-2 toxin impaired the mouse response to Reovirus suppressing immunoglobulin and interferon levels. Pestka, J.J. et al 200423 found the trichothecene Deoxynivalenol and others caused a dose response suppression of immunologic markers. Studies by Obremski, K. et al 201324 found T-2 toxin suppressed CD4, CD8 and CD21 levels in pig ileal Peyer’s patches. Wu, Q. et al 201825 reported downregulation of interferon, TGF-beta and Toll-like Receptors. There are similar immune deficits reported in ALS patients with subclass IgG deficiency26,27 and T-cell immune deficiency. Chronic low-dose poisoning of the immune system could evolve to create immune tolerance and immune evasion28,29. Immune evasion in ALS patients, could explain the recalcitrance to therapy. Monoclonal antibodies used in immunotherapy for oncology are being proposed as therapy for other diseases such as autoimmune disorders and chronic infections. If mycotoxins like T-2 toxin are causing immune evasion, then these new therapies could be promising in ALS.