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.