Children's Medical Center Corporation

Sanford-burnham Medical Research Institute

The Brigham and Women's Hospital, Inc.

Other

Yale University

Massachusetts Eye and Ear Infirmary

Burnham Institute for Medical Research

Neuromolecular, Inc.

Adamas Pharmaceuticals, Inc.

Panorama Research Inc.

Stuart A. Lipton

Evan B. Dreyer

Lipton, Stuart A.

Stuart Arthur Lipton

James W Larrick

Yuqiang Wang

Wenqing Ye

Jonathan S Stemler

Jonathan S Stamler

Evan B Dreyer

Shu-ichi Okamoto

Dongxian Zhang

Jon E Chatterton

Kevin A Sevarino

Marc Awobuluyi

Takumi Satoh

Xiaoming Zhang

Cyrus K Becker

Meenakshi S Venkatraman

Dean Le

Marcus Kaul

James V Manzione, Jr

Murat Digicaylioglu

The present disclosure provides adamantyl compounds having one or more amine groups and one or more nitrate groups. The aminoadamantyl nitrate compounds can be used to treat disorders of the central nervous system, including neurodegenerative and non-neurodegenerative diseases.

Aminoadamantyl nitrate compounds and their use to treat CNS disorders

Disclosed herein are methods for treating juvenile onset neurological conditions, such as autism (ASD), intellectual disability, or epilepsy, with an inhibitor of N-methyl-D-aspartate receptor (NMDAR). The inhibitor may be NitroSynapsin or a derivative thereof.

Methods and compositions for treating neurological conditions

Neurite outgrowth-promoting prostaglandins (NEPPs) and other electrophilic compounds bind to Keap1, a negative regulator of the transcription factor Nrf2, and prevent Keap1-mediated inactivation of Nrf2 and, thus, enhance Nrf2 translocation into the nucleus of neuronal cells. Therefore, neuroprotective compositions and related methods are provided that employ such neuroprotective compounds, and prodrugs of such compounds, to cause dissociation of Nrf2 from a Keap1/Nrf2 complex.

Neuroprotective compositions and methods

The present invention provides a method of differentiating progenitor cells to produce a population containing protected neuronal cells. A method of the invention includes the steps of contacting the progenitor cells with a differentiating agent; and introducing into the progenitor cells a nucleic acid molecule encoding a MEF2 polypeptide or an active fragment thereof, thereby differentiating the progenitor cells to produce a population containing protected neuronal cells. In one embodiment, the MEF2 polypeptide is human MEF2C or an active fragment thereof.

Methods of differentiating and protecting cells by modulating the p38/MEF2 pathway

The invention provides isolated N-methyl-D-aspartate type 3B (NR3B) polypeptides, functional fragments and peptides, encoding nucleic acid molecules and polynucleotides, and specific antibodies. Also provided are excitatory glycine receptors, containing either NR3B or NR3A polypeptides. Further provided are methods for detecting excitatory glycine receptor ligands, agonists and antagonists. The invention also provides related diagnostic and therapeutic methods.

Excitatory glycine receptors and methods

Methods of differentiating and protecting cells by modulating the P38/MEF2 pathway

The present invention provides a method of providing acute neuroprotection by inducing the erythropoietin (EPO) signaling pathway in neuronal cells close to or subsequent to the time of excitatory insult; and inducing an insulin-like growth factor (IGF) signaling pathway in the neuronal cells close to or subsequent to the time of excitatory insult, thereby producing a synergistic acute neuroprotective effect in the neuronal cells. The invention also provides a method of preventing or reducing the severity of a neurologic condition in a subject by administering to the subject EPO or an active fragment or analog thereof at a dose of at most 2000 U/kg; and administering to the subject an IGF or an active fragment or analog thereof, thereby providing neuroprotection and preventing or reducing the severity of the neurologic condition. Such a method can be used to prevent or reduce the severity of, for example, Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, amyotrophic lateral sclerosis, multiple sclerosis, a movement disorder, HIV-associated dementia, HIV-associated neuropathy, neuropathic pain, migraine, glaucoma, drug addiction, drug withdrawal, drug dependency, depression or anxiety.

Neuroprotective synergy of erythropoietin and insulin-like growth factors

The present invention provides novel aminoadamantane derivatives, methods of making the derivatives, compositions including the novel aminoadamantane derivatives, and methods for the treatment and prevention of neurological diseases using the derivatives and compositions There are a variety of neurological disorders that can be treated using the present invention, including, for example, the following: neurological disorders arising from trauma, ischemic or hypoxic conditions that can be treated include stroke, hypoglycemia, cerebral ischemia, cardiac arrest, spinal cord trauma, head trauma, perinatal hypoxia, cardiac arrest and hypoglycemic neuronal damage; neurodegenerative disorders such as epilepsy, Alzheimer's disease, Huntington's disease Parkinsonism, and amyotrophic lateral sclerosis; other diseases or disorders such as convulsion, pain, depression, anxiety, schizophrenia, muscle spasms, migraine headaches, urinary incontinence, nicotine withdrawal, opiate tolerance and withdrawal, emesis, brain edema, tardive dyskinesia, AIDS-induced dementia, ocular damage, retinopathy, cognitive disorders, and neuronal injury associated with HIV-infection such as dysfunction in cognition, movement and sensation.

Aminoadamantane derivatives as therapeutic agents

Purified human 68075, or a purified protein comprising at least a portion of the endogenous human 68075, is active in promoting regeneration of a central or peripheral neuron.

Protein 68075 and its use for regenerating nerve cell processes

The present invention provides novel aminoadamantane derivatives, methods of making the derivatives, compositions including the novel aminoadamantane derivatives, and methods for the treatment and prevention of neurological diseases using the derivatives and compositions. There are a variety of neurological disorders that can be treated using the present invention, including, for example, the following: neurological disorders arising from trauma, ischemic or hypoxic conditions that can be treated include stroke, hypoglycemia, cerebral ischemia, cardiac arrest, spinal cord trauma, head trauma, perinatal hypoxia, cardiac arrest and hypoglycemic neuronal damage; neurodegenerative disorders such as epilepsy, Alzheimer's disease, Huntington's disease Parkinsonism, and amyotrophic lateral sclerosis; other diseases or disorders such as convulsion, pain, depression, anxiety, schizophrenia, muscle spasms, migraine headaches, urinary incontinence, nicotine withdrawal, opiate tolerance and withdrawal, emesis, brain edema, tardive dyskinesia, AIDS-induced dementia, ocular damage, retinopathy, cognitive disorders, and neuronal injury associated with HIV-infection such as dysfunction in cognition, movement and sensation.

A method for identifying agents useful for protection of a human neuron from injury. The method includes the steps of providing a cell which has NMDA receptor; selecting a agent potentially useful for oxidation of the NMDA receptor; treating the cell with the agent; and determining whether the NMDA receptor is oxidized by the agent.

Using glutathiane to protect neurons from injury

The invention features methods of treating cytotoxic damage in a subject comprising administering to the subject a substance which is a complement inhibitor, free radical scavenger, or both, to thereby treat cytotoxic damage. The methods of the invention can be used to treat cytotoxic damage associated with a non-thrombotic or thrombotic condition. Methods of treating thrombotic conditions such as stroke and/or ischemia in a subject, comprise administering a thrombolytic agent and a substance which is a complement inhibitor, free radical scavenger or both.

Method of treating cytotoxic damage

Elevated glutamate levels are associated with glaucoma, and damage to retinal ganglion cells can be controlled by administering to the patient a compound capable of reducing glutamate induced excitotoxicity in a concentration effective to cause reduction of such excitotoxicity.

Growing community of inventors

Rancho Santa Fe, CA, United States of America

Stuart Arthur Lipton