Abstract: 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.

Abstract: 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.

Abstract: The invention is based on the discovery that rho kinase inhibitors can be used to treat pseudobulbar affect (PBA). The inventive methods relate to the use of rho kinase inhibitors in the treatment of patients with PBA. Preferred aspects of the invention contemplate treating PBA due to dementia, especially cortical dementia, such as AD, FTD and cortical vascular dementia.

Abstract: 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.

Abstract: 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.

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.

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.

Abstract: The invention relates to the treatment of neurodevelopmental disorders using an inhibitor of rho kinase. Preferred methods contemplate the treatment of infants and children. Certain embodiments involve treating a neurodevelopmental disorder is caused by defects of metabolism, including defects of amino acid transport or metabolism, acid-base balance, carbohydrate transport or metabolism, metal homeostasis, neurotransmitter metabolism, or fatty acid transport or metabolism. Methods address a variety of conditions caused by changes in the genetic material that affect the structure and/or expression of certain genes. Preferred methods treat Down syndrome, Fragile X syndrome, oligophrenin 1 deficiency, Rett syndrome, autistic disorder, Asperger's syndrome, pervasive developmental disorder not otherwise specified, and other autism spectrum disorders.

Abstract: The invention relates to the treatment of neurodevelopmental disorders using an inhibitor of rho kinase. Preferred methods contemplate the treatment of infants and children. Certain embodiments involve treating a neurodevelopmental disorder is caused by defects of metabolism, including defects of amino acid transport or metabolism, acid-base balance, carbohydrate transport or metabolism, metal homeostasis, neurotransmitter metabolism, or fatty acid transport or metabolism. Methods address a variety of conditions caused by changes in the genetic material that affect the structure and/or expression of certain genes. Preferred methods treat Down syndrome, Fragile X syndrome, oligophrenin 1 deficiency, Rett syndrome, autistic disorder, Asperger's syndrome, pervasive developmental disorder not otherwise specified, and other autism spectrum disorders.

Abstract: 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.

Abstract: The invention relates to the treatment of ascites, and especially refractory ascites, with an orally bioavailable prodrug of dopamine. A preferred prodrug of dopamine is docarpamine. In one embodiment treated patients are, prior to treatment, on doses of furosemide >80 mg/day and/or spironolactone >100 mg/day or equivalent doses of an alternative loop-acting and/or distal-acting diuretic. The ascites treated by the invention are typically caused by liver cirrhosis due to alcohol or non-alcoholic fatty liver disease and generally not due to viral hepatitis or primary biliary cholangitis. Typical patients have an activated renin-angiotensin-aldosterone levels as may be indicated by elevated levels of renin and/or aldosterone. Refractory ascites treatable according to the invention are such that patients beginning treatment require large volume paracentesis at a minimum of: (a) 3 times in 60 days, (b) 4 times in 90 days or (c) at least once every 30 days over a 90-day period.

Abstract: 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.

Abstract: Disclosed is a stable oral liquid pharmaceutical composition of trimetazidine having a pH of about pH 4 to about pH 8, comprising a therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof, one or more orally acceptable buffers, and one or more orally acceptable preservatives that is effective in said pH range. Also disclosed are methods of treating patients with stable oral liquid pharmaceutical composition. The phamaceutical composition is particularly suitable for treating a patient having a condition treatable by trimetazidine, such as cirrhosis and renal deficiency, and who has a decreased tolerance for acidic or highly basic oral solutions.

Abstract: Disclosed is a stable oral liquid pharmaceutical composition of trimetazidine having a pH of about pH 4 to about pH 8, comprising a therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof, one or more orally acceptable buffers, and one or more orally acceptable preservatives that is effective in said pH range. Also disclosed are methods of treating patients with stable oral liquid pharmaceutical composition. The pharmaceutical composition is particularly suitable for treating a patient having a condition treatable by trimetazidine, such as cirrhosis and renal deficiency, and who has a decreased tolerance for acidic or highly basic oral solutions.

Abstract: The invention relates to the surprising discovery that TMZ and pharmaceutical salts thereof are an effective pharmacological agent in the treatment of certain decompensating patients with an underlying chronic liver condition. In particular, TMZ or a pharmaceutical salt thereof is useful in treating cirrhosis patients having a Child Pugh score of at least 10, but not having a Child Pugh Score less than 10. In addition, TMZ or a pharmaceutical salt thereof is discovered to be useful in decompensating cirrhotics who are suffering from at least one organ system failure selected from the group consisting of hepatic, coagulation, renal, cerebral, circulatory and respiratory. Further to that, TMZ or a pharmaceutical salt thereof is useful in treating patients with acute-on-chronic liver.

Abstract: Disclosed is a stable oral liquid pharmaceutical composition of trimetazidine having a pH of about pH 4 to about pH 8, comprising a therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof, one or more orally acceptable buffers, and one or more orally acceptable preservatives that is effective in said pH range. Also disclosed are methods of treating patients with stable oral liquid pharmaceutical composition. The pharmaceutical composition is particularly suitable for treating a patient having a condition treatable by trimetazidine, such as cirrhosis and renal deficiency, and who has a decreased tolerance for acidic or highly basic oral solutions.

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.

Abstract: A method of treating or preventing amyloid related imaging abnormalities (ARIA) in patients receiving one or more course of medical treatment for Alzheimer's Disease includes administrating a SUR1-TRPM4 channel inhibitor, such as glyburide, in an amount effective to prevent the formation or reduce the size of one or more ARIAs in the brain.

Abstract: DNA encoding a therapeutically suitable glutaminase has been molecularly cloned. This allows one to obtain a polypeptide which is a therapeutically suitable glutaminase free of contaminating endotoxin. It has been found that this polypeptide is a potent anti-viral agent and when coupled to an anti-tumor monoclonal antibody is a potent anti-cancer agent. The gluatminase of the present invention is particularly useful for treating lung, breast and colon cancer cells and in the treatment of HIV-infected cells.

Abstract: Histidine ammonia lyase (HAL) isolated from Corynebacteriaceae can decrease serum histidine levels, induce accumulation of urocanic acid, and is not inhibited by L-histidinol. As a result, histidine ammonia lyases similar to the one isolated from Corynebacteriaceae are uniquely suitable for combination therapy with L-histidinol to treat histidine- and/or histamine-dependent pathologies, for example, infectious viruses, such as human Respiratory Syncytial Virus (RSV), Herpes Simplex Virus (HSV), and Human Immunodeficiency Virus (HIV), as well as cancers.