Small molecule therapeutic compounds that reduce the incidence of intracerebral hemorrhage and brain microhemorrhages
The described invention relates to small molecule therapeutic compounds capable of reducing the incidence of intracerebral hemorrhage and brain microhemorrhages identified using zebrafish and mouse models of intracerebral hemorrhage and brain microhemorrhages.
1. A method for reducing incidence of brain vascular leakage comprising administering to a subject in need thereof a pharmaceutical composition containing a small molecule therapeutic compound selected from artemether or a derivative of artemether, a therapeutic amount of which is effective to reduce incidence of bleeding in the brain by at least 30% relative to a control wherein the brain vascular leakage is brain microhemorrhage induced by administration of a statin, or the brain vascular leakage is a spontaneous intracerebral hemorrhage.
2. The method according to claim 1 , wherein the derivative of artemether is dihydroartemisinin, artemisinin, or artesunate.
3. The method according to claim 1 , wherein the vascular leakage is brain microhemorrhage induced by administration of a statin.
4. The method according to claim 3 , wherein the statin is atorvastatin.
5. The method according to claim 1 , wherein the vascular leakage is a spontaneous intracerebral hemorrhage.
6. The method according to claim 5 , wherein the spontaneous intracerebral hemorrhage occurs in association with a mutation of one or more genes selected from beta-pix, Pak2a, cdh5, ccm1, ccm2, ccm3, Rap1b, Pggt1b, Hmgcrb, and integrin beta3.
7. The method according to claim 1 , wherein the spontaneous intracerebral hemorrhage is due to brain vascular malformation a brain vascular malformation.
8. The method according to claim 7 , wherein the brain vascular malformation is a cerebral cavernous malformation.