Drug Eluting Embolization Coils for Improved Treatment of Intracranial Aneurysms

PROJECT SUMMARY Brain aneurysms are a high risk condition in which bulging blood vessels in the brain are at risk of ruptureThe mortality rate after rupture isif no treatment is administeredCurrent treatment for both ruptured and unruptured aneurysms includes surgical clippingexovascular therapyand catheter based interventionendovascular therapyIn endovascular therapywhich is the focus of this workplatinum coils are inserted into the aneurysm to induce clotting and exclude the aneurysm from circulationThe primary challenge associated with endovascular aneurysm therapy is the risk of aneurysm recurrence due to mechanical compaction and enzymatic digestion of the clot in the aneurysm sacRecurrence in intracranial aneurysms elevates the risk of hemorrhagic strokeThis proposal will evaluate the safety and efficacy of a drug eluting coil to improve outcomes when treating intracranial aneurysms prophylacticallyWe posit that sustained release of naturally occurring crosslinking agents delivered from drug eluting endovascular coils will increase the mechanical robustness of the clotsreduce fibrinolysisand ultimately reduce the risk of recurrenceClots with increased chemo mechanical stability will resist failure modes associated with coil compaction and enzymatic degradationThe safety and efficacy of genipin eluting coils will be evaluated in animal models that are clinically relevant and mimic the anatomy of defects in humansThe safety and efficacy of genipin eluting coils will be evaluated as a function of dosing and delivery kineticsIn vitro efficacy will be measured using a simulated coiled aneurysm in a model aneurysm sac operating under perfusionIn vivo experiments will be performed using a rabbit elastase aneurysm modelEfficacy will be quantified by angiographyhistologyand chemo mechanical measurements of thrombus in the aneurysmsThis project will ultimately measure the in vivo safety and efficacy of drug eluting coils as a potentially superior technology to treat unruptured anuerysmsFollow on clinical studies in humans will further establish the safety and efficacy of genipin eluting embolization coilsDrug eluting coils have the potential to transform the treatment of unruptured intracranial aneurysms and dramatically reduce the risk of hemorrhagic stroke PROJECT NARRATIVE Drug eluting coils will improve the chemo mechanical robustness of induced clots and reduce the risk of rupture in intracranial aneurysmsThis technology will ultimately reduce the long term risk of hemorrhagic stroke and increase the likelihood of positive clinical outcomes of intracranial aneurysms that are prophylactically treated through endovascular coiling