Methods of medical treatment with SUR1-TRPM4 channel inhibitors

Inventors

Jacobson, Sven • MacAllister, Thomas

Assignees

Remedy Pharmaceuticals Inc

Abstract

A method of treating or preventing adverse outcomes associated with tissue plasminogen activator (tPA) administration, cerebral edema-related side effects, cerebral edema associated with radiation therapy, or migraine headaches by administering an effective amount of a SUR1-TRPM4 channel inhibitor, such as glyburide, and optionally the co-administration of a second therapeutically active agent, to a subject in need thereof. Adverse outcomes associated with tPA include cerebral hemorrhage, cerebral edema, physical impairment or death. The administration of the SUR1-TRPM4 channel inhibitors occurs prior to the radiation therapy, during the radiation therapy, after the radiation therapy, or combinations thereof. The SUR1-TRPM4 channel inhibitor is administered prior to surgical excision of a brain tumor, CAR-T therapy, or administration of flutarabine. Alternatively, or in addition, the SUR1-TRPM4 channel inhibitor is administered prior the onset of the cerebral edema-related side effects.

Core Innovation

The invention relates to SUR1-TRPM4 channel inhibitors, including glyburide, for medical treatment methods that address adverse outcomes associated with tissue plasminogen activator (tPA) administration. The problem addressed is reduction of mortality resulting from tPA administration in a subject, including outcomes such as cerebral hemorrhage and cerebral edema.

The invention provides methods in which an effective amount of glyburide is administered to a subject that has been administered tPA, in order to reduce mortality. The approaches include administering glyburide before, simultaneously, or after tPA, including administration within a stroke-onset window.

The invention further describes use of SUR1-TRPM4 channel inhibition to reduce cerebral edema in connection with additional therapeutic contexts. These contexts include cerebral edema related to radiation therapy, cerebral-edema-related side effects from CAR-T therapy, flutarabine, and surgical excision of a brain tumor, and prevention or treatment of migraine headaches.

Claims Coverage

The partial content identifies one independent claim, which covers reducing mortality associated with tPA administration by administering an effective amount of glyburide. Dependent claims refine this coverage by adding pharmacokinetic/concentration targets and by specifying timing, subject selection, and dosage/range constraints.

Overall, the claim coverage centers on reducing mortality from tPA administration through glyburide administration, further constrained by concentration targets (steady-state and Cmax), timing relative to tPA, subject selection using ASPECTS, and a specified daily dosage range.

Stated Advantages

Documented Applications