This is interesting news for EGCG indeed. The authors already mention the caveats: poor oral availability, poor brain penetration. Moreover, EGCG displays promiscuous activity (BACE, 20 S proteasome) on many targets.

The small therapeutic window imposes another obstacle. The authors applied up to 100 μM concentrations (46 mg/l). This is dangerously close to the IC50 (IP) in mice, which is 100-125 mg/kg body weight (BW) for 24 h-72 h lethality. Kader Yagiz and colleagues examined this in a different line of transgenic mice: "When an amount of 150 or 250 mg/kg BW was injected intraperitoneally, EGCG was toxic to both transgenic and wild-type mice (Table 3). Mice from both groups were dead within 24 h. The EC50 for 24-h survival of wild-type mice was about 125 mg/kg BW of EGCG, but even at 100 mg/kg BW the animals died within 48 to 72 h." (From Yagiz et al., 2006.)

Despite the remarkable effects of EGCG, unfortunately it is not a lead for CNS drug development.

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