Biogen Chesapeake LLC

Remedy Pharmaceuticals, Inc.

Critical Care Diagnostics, Inc.

Woolsey Pharmaceuticals, Inc.

University System of Maryland

The United States Government As Represented by the Department of Veterans Affairs

Sven Jacobson

James V Snider

Thomas MacAllister

Thomas W Macallister

Robert Ang

Robert W Gerwien

J Marc Simard

Gillian Clarke

Rajinder Matharu

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 cmor less than 125 cmas 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.

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

Disclosed are methods of treating patients with AD using a rho kinase inhibitor. A preferred rho kinase inhibitor used according to the invention is fasudil, which is typically administered orally in a total daily dose of 70-140 mg. A preferred dosing regimen involves administering the daily dose in three equal portions throughout the day. Preferred methods continue for more than one month and typically at least 2 or 3 months. Some preferred methods do not treat mild cognitive impairment and patients have and MMSE score of ≤23 and/or a CDR-SOB score of ≥4.5.

Methods of using rho kinase inhibitors to treat alzheimer's disease

The present invention relates to the treatment of a sporadic ALS patient with oral fausdil at a dose of 180-240 mg/day. This results in an anticipated 25-50% reduction in the average decline over at least three months as measured using the revised ALS Functional Rating Scale.

Method of treating amyotrophic lateral sclerosis

This disclosure relates to the treatment of ischemic stroke at risk of brain swelling using SUR1-TRPM4 channel inhibitors. In some embodiments, the methods include treating patients suffering from a large hemispheric infarction. In certain embodiments, patients have a baseline NIHSS of ≤20. In other embodiments, patients have lesion volume of less than 140 cmor less than 125 cmas measured by MRI DWI or CTP. The patient may have suffered a wake-up stroke. Some embodiments involve treating patients who also undergo treatment with a thrombolytic agent and/or decompressive therapy.

The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.

Methods of intravenous administration of glyburide

The present technology is related to reducing or treating neurological swelling and related conditions with SUR1-TRPM4 channel inhibitors. In some embodiments, the methods include: reducing late neurological deterioration or preventing death, reducing cerebral midline shift, reducing the degree of disability in a subject, counteracting blood glucose levels in a subject receiving a SUR1-TRPM4 channel inhibitor, preventing brain swelling, monitoring liver enzyme activity along with treating injury or conditions related to CNS edema, or monitoring cardiac activity along with treating injury or conditions related to CNS edema.

Methods of treating injuries or conditions related to CNS edema

The invention is based on the discovery that rho kinase inhibitors, particularly fasudil can be used to treat agitation/anxiety in dementia patients, particularly Alzheimer's disease patients. Fasudil treatment of Alzheimer's patients resulted in improvements in agitation that are orders of magnitude to that observed with other potential therapeutic agents.

Methods of treating agitation and other dementia-associated behavioral symptoms

Disclosed are methods of treating patients with AD using a rho kinase inhibitor. A preferred rho kinase inhibitor used according to the invention is fasudil, which is typically administered orally in a total daily dose of 70-140 mg. A preferred dosing regimen involves administering the daily dose in three equal portions throughout the day. Preferred methods continue for more than one month and typically at least 2 or 3 months. Some preferred methods do not treat mild cognitive impairment and patients have and MMSE score of&#x2264;23 and/or a CDR-SOB score of&#x2265;4.5.

The invention is based on the discovery that rho kinase inhibitors can be used to treat certain dementia-associated wandering. The inventive methods relate to the use of rho kinase inhibitors in the treatment of patients with cortical dementia-associated wandering. Preferred aspects of the invention contemplate treating wandering due to cortical vascular dementia and wandering due to dementia where the patient is a persistent wanderer and/or where the patient does not display a wayfinding defect.

Methods of treating cortical dementia associated wandering

The invention is based on the discovery that rho kinase inhibitors can be used to treat proteinopathy associated wandering. A number of degenerative neurological diseases are thought to be caused, at least in part, by the formation of protein aggregates that cause neurotoxicity and progressive decline in function. The inventive methods related to the use of rho kinase inhibitors in the treatment of patients with proteinopathy-associated wandering. The patients may be suffering from Huntington's disease, a traumatic brain injury, autism spectrum disorder, Down syndrome or a proteinopathy-associated dementia, such as Alzheimer disease or frontotemporal dementia.

Methods of treating wandering in Lewy dody dementia

The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 &#x3bc;g/hr and about 300 &#x3bc;g/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.

The present invention relates to the treatment patient with a 4-repeat (4R) tauopathy using a therapeutically effect amount of a rho kinase inhibitor. One preferred inhibitor is fasudil and preferred methods involve the daily oral administration of between 20 and 250 mg of fasudil. Preferred 4R tauopathies treatable according to the invention include progressive supranuclear palsy with Richardson syndrome (PSP-RS) and corticobasal syndrome with probable sporadic corticobasal degeneration.

Methods of treating 4-repeat tauopathies

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.

Growing community of inventors

New York, NY, United States of America

Sven Jacobson