Table.

Overview of Putative Pre-clinical Pharmacologic Approaches

Potential Compound	Advantages	Disadvantages
BDNF	Potent Synaptic Growth Factor Expression regulated by MeCP2 Reversed or attenuated phenotypes in mutant mecp2 mice	Short half life Administration Blood-brain barrier permeability Specificity of target effect
BDNF-Mimetics	Similar to BDNF Crosses blood-brain barrier Reversed or attenuated phenotypes in mutant mecp2 mice	Effects in humans unknown Potential side effects Specificity of target effect New class of compounds with limited research
Insulin-Like Growth Factor-1	Crosses blood-brain barrier FDA approval for poor growth Reversed or attenuated phenotypes in mutant mecp2 mice	Mechanism of phenotype reversal unknown Potential side effects Specificity of target effect
Read-through Compounds Aminoglycosides Small Molecules	Corrects full length protein deficiency Reversed phenotypes in cell cultures models of RTT	Useful for limited RTT population with nonsense mutations Blood-brain barrier permeability unknown Renal and ototoxicity is a major problem with aminoglycosides Specificity for MeCP2 unknown Mis-expression of other genes that could be harmful