I am working to determine the proper therapeutic dose for certain antibody so I need to know how we can evaluate the toxicity using a validated method ?
Please, could anybody also provide me with a published article about this?
what about measuring the oxidative stress in the brain tissue, it may be act as a biomarker of neurotoxicty
First and foremost and I know this sounds basic. I would check the endotoxin, sodium and potassium levels of the antibodies and all the injection fluids. I have seen batches lyophilized antibodies with very high sodium levels that required dialysis. Rapid bolus of sodium can cause demyelinating events (when the sodium is already low...but being safe). Other than that it will be back to animal models, clinical statistics (look at the Bayesian inference for rare events or MCMC simulations) and pathological IHC validation of adverse reactions. Finally, there is always HPLC or GC /MS looking at urine biomarkers for brain specific lipids.
This is just some ideas. Hope this helps and good luck!
Try on culture cells first. But the first question is: what is/are the expected effect/s of your antibodies, i.e. what is/are the antigen/s they "attack" and where this/these antigen/s are located? Sincerely
https://www.researchgate.net/publication/254261121_The_toxicity_of_antiprion_antibodies_is_mediated_by_the_flexible_tail_of_the_prion_protein?ev=prf_pub
Article The toxicity of antiprion antibodies is mediated by the flex...
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