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Posted On: 05/26/2022 2:45:54 PM
Post# of 148889
Re: chuckles759 #123804
The linked article from 2013 concludes that IVIGG can deliver "therapeutically relevant" amounts of medicine to the brain.
But seems a little sketchy to me.
The amount of medicine delivered to the brain is less than one part in one thousand of the medicine delivered intravenously.
Maybe that is good enough, but i doubt it. Maybe things have improved since then.
Just seems like a pretty weak claim.
"We determined the percentage of injected IVIg migrating to the CNS to provide a quantitative assessment of the capacity of IVIg to interact with therapeutic targets within the brain. We report that 0.009±0.001% and 0.0017±0.0005% of systemically administered IVIg reached the cortex and hippocampus of animals after a single injection. Surprisingly, although IgG are commonly considered for the treatment of CNS diseases, very few quantitative data on their brain bioavailability can be found in the literature. Statements of ∼0.1% of injected IgG reaching the brain in the mouse are often made,21, 22 referring to results mentioned as data not shown in a report published in 200023 or measured from relative % of injected dose per gram of brain from a single time point (1 hour post injection).24 In most of these analyses, the concentration was obtained from biotinylated or radiolabeled injected Ig. As stated by Bard et al,19 it is unknown how much of the radioactive (or biotin) counts were associated with intact antibody and how much antibodies were engaged in the process of degradation. In contrast, here we performed human-specific enzyme-linked immunosorbent assay that requires intact Fc fragments. Additionally, a brain uptake of 0.06% injected dose per gram of tissue is reported using a radiolabeled rat mAb administered through the jugular vein, but with blood radioactivity included in the evaluation of brain IgG content.25 Thus, although the present percentage of injected IgG found in the brain after a systemic injection appears lower than traditionally accepted numbers, it is important to underscore that our assessment was calculated from the total dose of injected IVIg instead of plasma IgG at a specific time point. Our data also represent an absolute percentage of IgG (not per gram of brain tissue) and was measured after intracardiac perfusion to eliminate the blood from the brain vasculature. Nevertheless, extrapolating from these percentages and assuming comparable transport dynamics in humans, one can estimate that, from a 28 g injected dose,8 roughly 250 mg and 50 mg reach the cortex and hippocampus, respectively. This would correspond to concentrations approximating 10−7 to 10−5 mol/L of cerebral interstitial fluids. The interaction between monoclonal antibodies and antigens display high specificity and affinity, with equilibrium dissociation ranging from 10−11 to 10−4 mol/L.26, 27 Therefore, if we assume similar affinity of IVIg for CNS targets, the brain concentrations measured here after systemic injections are therapeutically relevant."
But seems a little sketchy to me.
The amount of medicine delivered to the brain is less than one part in one thousand of the medicine delivered intravenously.
Maybe that is good enough, but i doubt it. Maybe things have improved since then.
Just seems like a pretty weak claim.
"We determined the percentage of injected IVIg migrating to the CNS to provide a quantitative assessment of the capacity of IVIg to interact with therapeutic targets within the brain. We report that 0.009±0.001% and 0.0017±0.0005% of systemically administered IVIg reached the cortex and hippocampus of animals after a single injection. Surprisingly, although IgG are commonly considered for the treatment of CNS diseases, very few quantitative data on their brain bioavailability can be found in the literature. Statements of ∼0.1% of injected IgG reaching the brain in the mouse are often made,21, 22 referring to results mentioned as data not shown in a report published in 200023 or measured from relative % of injected dose per gram of brain from a single time point (1 hour post injection).24 In most of these analyses, the concentration was obtained from biotinylated or radiolabeled injected Ig. As stated by Bard et al,19 it is unknown how much of the radioactive (or biotin) counts were associated with intact antibody and how much antibodies were engaged in the process of degradation. In contrast, here we performed human-specific enzyme-linked immunosorbent assay that requires intact Fc fragments. Additionally, a brain uptake of 0.06% injected dose per gram of tissue is reported using a radiolabeled rat mAb administered through the jugular vein, but with blood radioactivity included in the evaluation of brain IgG content.25 Thus, although the present percentage of injected IgG found in the brain after a systemic injection appears lower than traditionally accepted numbers, it is important to underscore that our assessment was calculated from the total dose of injected IVIg instead of plasma IgG at a specific time point. Our data also represent an absolute percentage of IgG (not per gram of brain tissue) and was measured after intracardiac perfusion to eliminate the blood from the brain vasculature. Nevertheless, extrapolating from these percentages and assuming comparable transport dynamics in humans, one can estimate that, from a 28 g injected dose,8 roughly 250 mg and 50 mg reach the cortex and hippocampus, respectively. This would correspond to concentrations approximating 10−7 to 10−5 mol/L of cerebral interstitial fluids. The interaction between monoclonal antibodies and antigens display high specificity and affinity, with equilibrium dissociation ranging from 10−11 to 10−4 mol/L.26, 27 Therefore, if we assume similar affinity of IVIg for CNS targets, the brain concentrations measured here after systemic injections are therapeutically relevant."
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