Therapy for subarachnoid hemorrhage and ischemia

Inventors

Tymianski, Michael

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 relates to methods of treating a subarachnoid hemorrhage in a human subject by administering an agent that binds to PSD-95 and inhibits binding of PSD-95 to an NMDAR2B subunit. The method is directed to inhibiting development of neurocognitive deficits in the subject, and the administering is not in the course of a clinical trial.

The disclosed approach is further framed around targeting PSD-95 binding to an NMDAR2 subunit, including NMDAR2B/NR2B, by using a PSD-95/NMDAR2-binding agent. The invention is associated with clinical-trial support (ENACT) and with outcomes described using MRI lesion burden (DWI/FLAIR) and neurological and neurocognitive/neuropsychiatric measures, including NIHSS and modified Rankin Scale (mRS).

The document also describes that the treatment can be applied in contexts involving intracranial aneurysms affecting the CNS, including endovascular repair, and that the benefit is stratified by prior aneurysm rupture. The targeting and intended effect are tied to inhibiting PSD-95/NMDAR2B binding to reduce lesion burden and improve neurological outcomes while supporting safety characterization with minimal drug-related adverse events and reduced procedural pain.

Claims Coverage

The partial content provides one independent claim. It includes a single core inventive concept: treating subarachnoid hemorrhage by administering a PSD-95 binding agent that inhibits PSD-95 binding to an NMDAR2B subunit to inhibit neurocognitive deficits, with administration not in the course of a clinical trial.

Across the provided independent claim, the inventive coverage centers on PSD-95 binding inhibition of PSD-95 to an NMDAR2B subunit to inhibit development of neurocognitive deficits in subarachnoid hemorrhage, with administration occurring outside a clinical trial.

Stated Advantages

Documented Applications