249 results about "Demyelinations" patented technology

The present invention provides methods and compositions for the production of glial cells and oligodendrocytes from placenta stem cells. The invention further provides for the use of these glia and oligodendrocytes in the treatment of, and intervention in, for example, trauma, ischemia and degenerative disorders of the central nervous system (CNS), particularly in the treatment of demyelinating diseases such as multiple sclerosis.

The present specification provides RXR agonists with both remyelination promotion and immunomodulatory activities, compositions comprising such RXR agonists, and methods using such compounds and compositions to treat a demyelination-related disorder by both promoting remyelination of neurons and modulating the immune system.

The present invention relates to the use of creatine compound and neuroprotective combinations including creatine, creatine phosphate or analogs of creatine, such as cyclocreatine, for treating diseases of the nervous system. Creatine compounds in combination with neuroprotective agents can be used as therapeutically effective compositions against a variety of diseases of the nervous system such as diabetic and toxic neuropathies, peripheral nervous system diseases, Alzheimer disease, Parkinson's disease, stroke, Huntington's disease, amyotropic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, dysmyelination and demyelination disorders, and mitochondrial diseases. The creatine compounds which can be used in the present method include (1) creatine, creatine phosphate and analogs of these compounds which can act as substrates or substrate analogs for creatine kinase; (2) bisubstrate inhibitors of creatine kinase comprising covalently linked structural analogs of adenosine triphosphate (ATP) and creatine; (3) creatine analogs which can act as reversible or irreversible inhibitors of creatine kinase; and (4) N-phosphorocreatine analogs bearing non-transferable moieties which mimic the N-phosphoryl group.

A statistical and functional correlation strategy to identify changes in cellular pathways specifically linked to impaired cognitive function with aging. Analyses using the strategy identified multiple groups of genes expressed in the hippocampi of mammals, where the genes were expressed at different levels for several ages. The aging changes in expression began before mid-life. Many of the genes were involved in specific neuronal and glial pathways with previously unrecognized relationships to aging and / or cognitive decline. The processes identified by the strategy suggest a new hypothesis of brain aging in which initially decreased neuronal activity and / or oxidative metabolism trigger separate but parallel genomic cascades in neurons and glia. In neurons, the cascade results in elevations in calcium signaling and reductions of immediate early gene signaling, biosynthesis, synaptogenesis and neurite remodeling. In contrast, glia undergo increased lipid metabolism and mediate a cycle of demyelination and remyelination that induces antigen presentation, inflammation, oxidative stress and extracellular restructuring. These identified genes and the proteins they encode can be used as novel biomarkers of brain aging and as targets for developing treatment methods against age-related cognitive decline, Alzheimer's Disease and Parkinson's Disease.

Therapeutic methods, therapeutic combinations and pharmaceutical compositions provided herein are useful for inhibiting demyelination, for delaying the clinical onset of a demylination condition, for inhibiting progression and / or reducing frequency of relapse of a demylination condition, and / or enhancing physical ability of a human subject having a demylination condition. Lacosamide is one of the active compounds.

The invention discloses a family of peptides termed NRP compounds or NRPs that can promote neuronal migration, neurite outgrowth, neuronal proliferation, neural differentiation and / or neuronal survival, and provides compositions and methods for the use of NRPs in the treatment of brain injury and neurodegenerative disease. NRP compounds can induce neurons and neuroblasts to proliferate and migrate into areas of damage caused by acute brain injury or chronic neurodegenerative disease, such as exposure to toxins, stroke, trauma, nervous system infections, demyelinating diseases, dementias, and metabolic disorders. NRP compounds may be administered directly to a subject or to a subject's cells by a variety of means including orally, intraperitoneally, intravascularly, and directly into the nervous system of a patient. NRP compounds can be formulated into pharmaceutically acceptable dose forms for therapeutic use. Methods for detecting neural regeneration, neural proliferation, neural differentiation, neurite outgrowth and neural survival can be used to develop other neurally active agents.

Disclosed are NgR proteins and biologically active Nogo (ligand) protein fragments. Also disclosed are compositions and methods for modulating the expression or activity of the Nogo and NgR protein. Also disclosed are peptides which block Nogo-mediated inhibition of axonal extension. The compositions and methods of the invention are useful in the treatment of cranial or cerebral trauma, spinal cord injury, stroke or a demyelinating disease.

A pharmaceutical for prevention and treatment of demyelination-associated neural function impairing diseases contains erythropoietin as an active ingredient, and protectively act on the survival of oligodendrocytes, which form a myelin sheath, in cerebrovascular dementia typified by multiple sclerosis and Binswanger disease, diseases involving demyelination. The pharmaceutical and method also promote maturation of undifferentiated oligodendrocytes present in the brain, activating remyelination. Through these mechanisms, the pharmaceutical and method can prevent and treat demyelination-associated neural function impairing diseases.

The present invention relates to a method and kit for in vitro diagnosing a complex disease such as cancer, in particular, acute myeloid leukemia (AML), colon cancer, kidney cancer, prostate cancer; transient ischemic attack (TIA), ischemia, in particular stroke, hypoxia, hypoxic-ischemic encephalopathy, perinatal brain damage, hypoxic-ischemic encephalopathy of neotatals asphyxia; demyelinating disease, in particular, white-matter disease, periventricular leukoencephalopathy, multiple sclerosis, Alzheimer and Parkinson's disease; in a biological sample. For the diagnosis, use is made of measuring at least two different species of biomolecules and classifying the results by means of suitable classifier algorithms and other statistical procedures. With the present invention, a significant improvement of the reliability of e.g. expression profiles alone, are achieved. In other words, in a defined collective, an up to 100% accurate positive diagnosis could be achieved, which renders the method of the present invention superior over the prior art.

The present invention relates to Spirocyclic Azetidinone Compounds, compositions comprising a Spirocyclic Azetidinone Compound and methods for treating or preventing a disorder of lipid metabolism, pain, diabetes, a vascular condition, demyelination or nonalcoholic fatty liver disease, comprising administering to a patient an effective amount of a Spirocyclic Azetidinone Compound.

Contemplated compositions and methods are directed to prevent and / or treat various autoimmune diseases that are typically associated with glycan dysregulation, and especially autoimmune demyelinating diseases. Further especially contemplated aspects include animal models and systems for screening compounds to treat and / or prevent such diseases.

The present disclosure relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same. The disclosure further concerns the use of such compounds in the treatment and / or prevention of certain types of cancers, pain, inflammation, restenosis, atherosclerosis, psoriasis, thrombosis, Alzheimer's, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination.

The present invention is based on the discovery that oligodendrocyte-myelin glycoprotein (OMgp), which is ex-pressed by oligodendrocytes and CNS myelin, negatively regulates oligodendrocyte and neuronal differentiation and survival. Based on these discoveries, the invention relates generally to methods of promoting neuronal and oligodendrocyte survival and differentiation by administration of an OMgp anatagonist. Additionally, the invention generally relates to methods of treating various diseases, disorders or injuries associated with demyelination, dysmyelination, oligodendrocyte / neuronal cell death, axonal injury and / or differentiation by the administration of an OMgp antagonist.

The present disclosure relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same, said compounds being capable of inhibiting or antagonizing TrkA receptor tyrosine kinases. In some aspects, the disclosure provides a compound having a structural formula (I):The disclosure further concerns the use of such compounds in the treatment and / or prevention of certain types of cancers, pain, inflammation, restenosis, atherosclerosis, psoriasis, thrombosis, Alzheimer's, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination.

Provided are non-human animal model systems for viral pathogenesis of neurodegeneration, autoimmune demyelination, and autoimmune diseases such as diseases of the central nervous system, including multiple sclerosis (MS), and diabetes. Such non-human animal model systems may be suitably employed for the study of diseases such as MS and diabetes and for the identification and characterization of candidate therapeutic compounds and compositions for the treatment of such diseases. Also provided herein are markers and methods for the detection, in patients susceptible to autoimmune disease, of autoimmune diseases of the central nervous system such as progressive multifocal leukoencephalopathy (PML) following treatment with one or more therapeutic agent as exemplified herein by the therapeutic agent natalizumab. Exemplary animal model systems comprise marmosets infected with a herpesvirus such as HHV6-A and HHV6-B, transgenic mouse and zebrafish animal model systems wherein the transgene encodes CD46, and methods for monitoring the risks of patients having MS, diabetes and other auto-immune disorders treated with anti-adhesion molecules such as natalizumab.

The application provides for methods and compositions for inhibiting demyelination, promoting remyelination and / or treating paralysis in a subject in need thereof. Preferably, such compositions include immunoglobulins (e.g., antibodies, antibody fragments, and recombinantly produced antibodies or fragments), polypeptides (e.g., soluble forms of the ligand proteins for integrins) and small molecules, which when administered in an effective amount inhibits demyelination and / or promotes remyelination in a patient. The compositions and methods described herein can also utilize other anti-inflammatory agents used to palliate conditions and diseases associated with demyelination.

The invention provides methods for producing myelin forming cells from multipotent self-renewing central nervous system neural stem cells as well as methods of using one or more cells from a multipotent self-renewing central nervous system neural stem cell population to form patches of myelin. Also provided are cell culture systems for forming patches of myelin and methods of treating demyelination diseases in a mammal.

Methods of treating neurological disorders, e.g., those characterized by demyelination and / or axonal loss (e.g., MS), are provided. The methods comprise administration of a therapeutically effective amount of at least one compound of Formula I:wherein R1 and R2 are independently selected from OH, O−, and (C1-6)alkoxy, or a pharmaceutically acceptable salt thereof; and either glatiramer acetate or interferon-beta.

This invention is in the field of neurology. Specifically, the invention relates to the discovery and characterization of molecular components that play a role in neuronal demyelination or remyelination. In addition, the invention relates to the generation of an animal model that exhibits hypomyelination. The compositions and methods embodied in the present invention are particularly useful for drug screening and / or treatment of demyelination disorders.

Antibodies, and particularly human antibodies, are disclosed that demonstrate activity in the treatment of demyelinating diseases as well as other diseases of the central nervous system that are of viral, bacterial or idiopathic origin, including neural dysfunction caused by spinal cord injury. Neuromodulatory agents are set forth that include and comprise a material selected from the group consisting of an antibody capable of binding structures or cells in the central nervous system, a peptide analog, a hapten, active fragments thereof, agonists thereof, mimics thereof, monomers thereof and combinations thereof. The neuromodulatory agent has one or more of the following characteristics: it is capable of inducing remyelination; binding to neural tissue; promoting Ca−− signaling with oligodendrocytes; and promoting cellular proliferation of glial cells. Amino acid and DNA sequences of exemplary antibodies are disclosed. Methods are described for treating demyelinating diseases, and diseases of the central nervous system of humans and domestic animals, using polyclonal IgM antibodies and human monoclonal antibodies sHIgm22(LYM 22), sHIgm46(LYM46) ebvHIgM MSI19D10, CB2bG8, AKJR4, CB2iE12, CB2iE7, MSI19E5 and MSI10E10, active fragments thereof and the like. The invention also extends to the use of human antibodies, fragments, peptide derivatives and like materials, and their use in diagnostic and therapeutic applications, including screening assays for the discovery of additional antibodies that bind to cells of the nervous system, particularly oligodendrocytes.

A method of diagnosis is disclosed. The method comprises using a display device for presenting a motion perception test to a subject and determining a subject response to the motion perception test. The response can be used for assessing presence or absence of demyelination and / or remyelination.

The present invention provides a composition and method for treating diseases associated with demyelination of the nerves, such as ALS, RA, Tremors / Parkinson's Disease, and MS, Alzheimer's disease, ALS, Guillain-Barre syndrome, atherosclerosis, schizophrenia, Tremors / Parkinsons's disease, senile dementia, Muscular Dystrophy, Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder, Complex Regional Pain Syndrome, Diabetes, Neuropathic Pain, Spider Arthritis West Nile Virus, Fibromyalgia, Shingles, Gout, Migraine Headaches, Post Polio Syndrome, Central Virus Deafness, Asthma, Chronic Pain Of Unknown Origin and Hepatitis C and for treating non-viral based cancers. By administering measured doses of an immunity-provoking agent and a bacterial antigen activator, patients suffering from ALS, RA, MS, Tremors / Parkinson's Disease, and prostate cancer and others realized immediate beneficial results with no side effects.

The present invention provides a selected population of neural cells, including neural stem cells, neural progenitor cells, neural precursor cells, and progeny thereof, which neural cells are selected for an apoE4− phenotype. In some embodiments, the neural cells are further selected for an apoE3+ phenotype. The selected population of neural cells is useful in treating various disorders, such as neurodegenerative disorders and demyelination diseases. The present invention further provides methods of treating neurodegenerative disorders and demyelinating diseases, generally involving administering a subject selected cell population.

The invention provides a method of treating a subject afflicted with a disease associated with demyelination of the central nervous system comprising administering to the subject a therapeutically effective amount of any of a composition containing Tripterygium wilfordii Hook F. root extract or components thereof and a pharmaceutically effective carrier in an amount effective to treat the subject.

The invention discloses a method for inducing differentiation from human mesenchymal stem cells to oligodendrocyte. The invention aims to provide a method for obtaining a large quantity of oligodendrocyte and using the oligodendrocyte to treat diseases such as myelin sheath damage or demyelination. The method is to obtain a large quantity of the autogenous human mesenchymal stem cells by a simple platy adhesion method, and to use adhesion molecules F3 / Contactin to induce differentiation from the human mesenchymal stem cells to the oligodendrocyte. The method adopts an easy, simple and convenient means to perform in vitro regulation on differentiation from the human mesenchymal stem cells to the oligodendrocyte, and achieves the aims of acquisition of the autogenous oligodendrocyte, preparation of a large quantity of the autogenous oligodendrocyte, and low cost. The method realizes the aim of applying the oligodendrocyte from the autogenous human mesenchymal stem cells to treat the demyelination disease, and has better economic benefit and social benefit.

A method for treatment of neurodegenerative disease conditions stemming from multiple sclerosis, aging, autoimmune diseases and fibromyalgia. A compound effective to increase neuronal metabolism of histamine to a histamine H2 agonist is administered in an amount sufficient to stimulate production of cyclic AMP at a level which is sufficient to maintain myelin against undergoing self-degeneration. The compound is selected from the group consisting of histamine M-methyltransferase, monoamineoxidase-A, monoamineoxidase-A agonists and histamine H3 antagonists. The histamine M-methyltransferase may be administered to increase neuronal metabolism of histamine to tele-methylhistamine, whereas the monoamineoxidase-A or monoamineoxidase-A agonist may be administered so as to increase neuronal metabolism of telemethylhistamine to an H2 agonist. Separately or in conjunction with the others, the histamine H3 antagonist may be administered so as to inhibit metabolism of the telemethylhistamine to an H3 agonist, thereby increasing metabolism of the telemethylhistamine to an H2 agonist. The increased histamine H2 agonist levels reduce demyelination and the symptoms that are associated with these conditions.

The present invention provides a non-toxic therapy and a novel use for Bowman Birk Inhibitor (BBI), as administered in Bowman Birk Inhibitor Concentrate (BBIC), for the treatment of autoimmune diseases in a patient, wherein the disease is characterized by chronic inflammation, such as rheumatoid arthritis; and more particularly for the treatment of those diseases that are characterized by chronic neuroinflammation and / or demyelination, such as Multiple Sclerosis (MS) and Guillain Barre Syndrome (GBS). In addition, the present invention provides methods for using BBI / BBIC to reduce, inhibit, suppress or prevent the chronic inflammation in such patients; and more particularly, to reduce, inhibit, suppress or prevent the chronic neuroinflammation and demyelination that occurs when the patient's nerve tissue is affected by the disease.

The cell death inhibitor comprising a substance capable of binding to macrophage migration inhibitory factor is useful as a preventive / therapeutic agent for, e.g., heart diseases, neurodegenerative diseases, cerebrovascular diseases, central nervous infections, traumatic diseases, demyelinating diseases, bone / joint diseases, kidney diseases, liver diseases, myelodysplastic diseases, arteriosclerosis, diabetes, pulmonary hypertension, sepsis, inflammatory bowel diseases, autoimmune diseases, failure accompanying rejection in organ transplantation, AIDS, cancer, etc.