Therapy for subarachnoid hemorrhage and ischemia

Inventors

Tymianski, Michael • Garman, Jonathan David

Assignees

NoNO Inc

Abstract

The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefiting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.

Core Innovation

The invention provides a method of screening a compound for activity useful in treating or effecting prophylaxis of stroke or hemorrhage in or otherwise affecting the central nervous system. The method is carried out by administering the compound to humans undergoing an endovascular repair procedure affecting the central nervous system, and comparing the result with a negative control.

The screening determination is performed by MRI imaging, wherein the MRI imaging includes DWI and FLAIR MRI. The method determines whether the compound reduces the number of infarcts resulting from the endovascular procedure compared with the negative control.

In the MRI assessment, the number of infarcts resulting from the endovascular procedure is determined by identifying infarcts at the same spatial location present on both DWI and FLAIR MRI. This spatially matched DWI/FLAIR infarct identification is used as the basis for evaluating whether the compound produces a reduction in infarct number.

Claims Coverage

The partial content includes one independent claim. It specifies an inventive screening method with two main MRI-linked features: reduction of infarct number after an endovascular CNS repair procedure versus a negative control, and infarct counting by spatially matching DWI and FLAIR lesion locations.

Overall, the claim coverage is focused on a human-screening approach for CNS stroke/hemorrhage utility that uses MRI (DWI/FLAIR) and spatially matched infarct identification to determine whether a compound reduces infarct number relative to a negative control.

Stated Advantages

Documented Applications