Methods of treating ischemic stroke at risk for cerebral or cerebellar edema

Inventors

Jacobson, Sven Martin • MacAllister, Thomas W.

Assignees

Remedy Pharmaceuticals Inc

Abstract

The invention relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors in combination with mechanical thrombectomy. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a lesion volume of less than 140 cm3 or less than 125 cm3 as measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo decompressive therapy.

Core Innovation

The invention improves outcomes in a patient diagnosed with an ischemic stroke in which outcomes are assessed by Modified Rankin Scale (mRS) scores. The patient has experienced a wake-up stroke, and the method comprises administering a SUR1-TRPM4 channel inhibitor. The treatment is coordinated with mechanical thrombectomy by defining whether the patient has undergone mechanical thrombectomy before administering or whether administering begins prior to or during mechanical thrombectomy.

A further aspect treats ischemic stroke in a patient that has experienced a wake-up stroke by treating with a therapeutically effective amount of a SUR1-TRPM4 inhibitor, where the treatment begins prior to a mechanical thrombectomy or begins during or after a mechanical thrombectomy. Patient selection is constrained by lesion volume limitations and, where described, by imaging selection using computed tomography perfusion or magnetic resonance imaging.

The invention also addresses improving outcomes for patients having a wake-up stroke or a large hemispheric infarction by administering a SUR1-TRPM4 channel inhibitor when the lesion volume is greater than 50 cm3 and less than 125 cm3. In related treating methods, the invention includes treatment begin timing relative to mechanical thrombectomy and, in some embodiments, specifies a SUR1-TRPM4 inhibitor selected from listed SUR1-TRPM4-interacting compounds, including glyburide and glibenclamide.

Claims Coverage

The independent claims cover methods for improving or treating ischemic stroke in wake-up stroke (and, in some claims, large hemispheric infarction) by administering a SUR1-TRPM4 channel inhibitor with specific timing relative to mechanical thrombectomy, and in narrower forms by adding lesion volume thresholds and/or imaging and other eligibility constraints. The independent inventive features are expressed in four independent claims identified as clm-00001, clm-00012, clm-00025, and clm-00027.

Across the independent claims, the core claim coverage is directed to administering or treating with a SUR1-TRPM4 channel inhibitor in wake-up stroke patients, with the key inventive structure defined by the timing of inhibitor treatment relative to mechanical thrombectomy, and in narrower independent claims by lesion volume limits in the range greater than 50 cm3 and less than 125 cm3 (and by extension, wake-up stroke or large hemispheric infarction contexts).

Stated Advantages

Documented Applications