It appears that the Hh agonist is having side effects at the current dose in animal models. There has been zero published articles that used a Hh agonist systemically.

What they have found is that the hedgehog pathway is turned on when tissue is damaged and repaired. Furthermore the Hh protein is preferentially up regulated in these tissue(s). Curis has said that when they induce stroke in animal models the Hh protein is up regulated in brain, potentially meaning a somewhat specific target for thier small molecule in the stroke model. However, because when you turn on the pathway it makes cells divide you have provide a way of making sure your molecule targets the correct tissue. They are not trying to make cells divide in the stroke model but what happens in low doses it actually prevents cells from dying. So the molecule acts a neuroprotective agent. There have been NO third party studies done with a stroke model and an agonist. The hard part with the agonist for stroke is, give enough to allow the cells to stay alive but not to cause abnormal proliferation. IMO it is not surprising they saw side effects, even the hair growth application uses a one time dose of an agonist. So with a systemic application of an agonist there is a fine line between helping ppl and side effects.