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1c), as excessive membrane affinity hinders efficient transmembrane passage to reach intracellular targets, directly impairing degradation activity even when the warhead is optimized

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This may contribute to the prolonged perception of pain

A study conducted in 2016 thus came to the following conclusion: If we had restricted the treatment of symptomatic patients to patients with both low serum levels and elevated metabolite levels, 63% of patients who responded well to the therapy would not have received treatment [] Only 16% of patients with good clinical improvement from vitamin B12 therapy had low serum levels and 54% of patients with good clinical improvement from vitamin B12 therapy had serum levels higher than 300 pg/mL. Some experts thus advise high-dose B12 treatment to treat all known nervous symptoms associated with B12 deficiency