Discussion
brain injuries, stroke, AIS, ischemic damage, infarct
EPP, ADVERSE EVENTS, STROKE, MINOR, INFLAMMATION, ADVERSE EFFECTS, ADVERSE DRUG REACTIONS, INFARCT
Our phase IIa clinical trial shows that administration of afamelanotide 16 mg implant in AIS patients is safe and well tolerated. This is the first time afamelanotide has been evaluated in AIS patients. Afamelanotide also appears to be associated with meaningful neurological recovery and radiological improvement of salvageable tissue.None of our patients had any serious adverse drug reactions. Minor, transient adverse events where present, were considered to be likely unrelated to afamelanotide. The minor adverse events were also very different between patients, suggesting afamelanotide was an unlikely cause. Afamelanotide is currently licenced in United States, Europe and Australia for treatment of EPP. Post marketing surveillance over several years has confirmed the positive safety profile of afamelanotide with no significant drug related adverse effects [Four of six patients showed reduction in the radiological measurements of infarct core on D3 and all surviving patients showed improvement in NIHSS at 42 days. Although the measurements of CT perfusion on D0 and MRI-FLAIR on D3 are not directly comparable, the direction and magnitude of reduction in infarct core volume was clearly evident. A repeat CT perfusion on D3 would risk unnecessary radiation and contrast related adverse effects while an MRI on D0 is not always practical. The reduction in core volume was also despite of a median time to treatment from stroke onset of 20 h. Neuroprotective agents are likely to result in better outcomes when given early in the process of ischemic damage and inflammation. However our data suggest that even at a median of 20 h, afamelanotide may provide benefit. A broad therapeutic window and longer lasting treatment effect with α-MSH hormone on AIS had been demonstrated in animal studies [The benefit of afamelanotide in AIS is likely due to its neuroprotective properties on the BBB. Neuroprotective agents, targeting tight junctions of BBB may confer vascular protection during AIS and other brain injuries [Afamelanotide may also have positive effects on AIS and other brain injuries through a direct neuromodulatory and neurotropic effect on melanocortin receptors [