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Furthermore, the threshold effect is consistent with the concept that methionine synthase activity may become saturated beyond a certain B12 concentration [17], explaining the diminishing returns observed at higher levels

What is missing There is no published human pharmacokinetic study of subcutaneous AOD-9604, no published human topical or intranasal exposure data, no Phase 3 efficacy trial, no long-term safety data beyond 24 weeks, and no published human cartilage or joint outcome data