142 results about "Dopaminergic" patented technology

The present application relates to the use of rotigotine or salts and prodrugs thereof for the manufacture of a medicament for the treatment or prevention of dopaminergic cell destruction in diseases associated with increased dopaminergic cell destruction. In particular, the present application also relates to the use of rotigotine as a drug for the preventive treatment of Parkinson's disease.

The present invention relates to methods and compositions for reducing Distress Dysfunction by restoring and maintaining homeostatic balance in the neurotransmitter systems underlying the Stress Response and the experience of distress and hedonic tone. Distress Dysfunction refers to the experience of dysfunctional emotional and physical distress that interferes with the individual's quality of life and functioning. A novel understanding of the bimodal opioid modulation of pain, and its impact, through serotonergic, dopaminergic, epinephrinergic, and norepinephrinergic processes, on hedonic tone, leads directly to new generation pharmaceutical formulations that are remarkably safe and effective for the treatment of a wide variety of Distress Dysfunctions, including anxiety, depression, anger, insomnia, mood disorders, eating disorders, sexual problems, pain, substance and behavioral addictions, gastrointestinal disorders, autistic spectrum disorders, attention-deficit and hyperactivity disorders, and other emotional and physical distress disorders. The foundation of this discovery is the power of Receptor Switchers, such as ultra-low-dose and very-low-dose opioid antagonists and GM1 ganglioside attenuators, in blocking acute and protracted excitatory opioid receptor signaling. Co-administration of Receptor Switchers with Endorphin Enhancers, such as specific cAMP PDE inhibitors and excitatory amino acids, is an excellent formulation for restoring healthy homeostatic balance to the endogenous opioid system, using the body's endorphins to reduce emotional and physical distress, and through synergistic and homeostatic processes, restoring positive hedonic tone. The addition of Synergistic Enhancers, such as amino acids, SSRI and SNRI agents, and non-opioid analgesics, as well as Exogenous Opioids, enhances and prolongs these therapeutic benefits. The novel principles discovered by this invention also teach a new generation of safe and effective formulations for the treatment of respiratory conditions, neuropathy, and nociceptive pain.

The present invention relates to a new phenylboronic-acid-functionalized graphene oxide composite nano material and preparation and application thereof. The material is prepared by immobilization of polydopamine-packed magnetic nanoparticles onto polyethyleneimine-modified graphene oxide and further introduction of phenylboronic acid monomers with carboxyl by amino of polyethyleneimine, and finally the material is used for enrichment of glycoproteins. The specific process is as follows: firstly, Fe3O4 magnetic nanoparticles are prepared by a solvothermal method, and auto polymerization of polydopamine can be performed on surface of the Fe3O4 magnetic nanoparticles under alkaline conditions; the magnetic graphene oxide composite nano material can be prepared by hydrogen bond and PI-PI interaction between the polydopamine and graphene oxide, then the positively charged polyethyleneimine is immobilized onto the surface of the negatively charged magnetic graphene oxide by electrostatic self-assembly; and finally the phenylboronic-acid-functionalized magnetic graphene oxide composite nano material can be prepared by introduction of the phenylboronic acid monomers by amidation reaction, and the phenylboronic-acid-functionalized magnetic graphene oxide composite nano material is successively used in the enrichment of the glycoproteins in bioanalysis.

Methods are provided for efficient production of midbrain dopaminergic (DA) neurons. In some aspects, methods involve differentiation and selection of DA neurons for a transgenic pluripotent cell population (e.g., cells comprising a selectable marker gene). Cell populations produced by the instant methods and methods of their use are likewise provided.

A cell system for treating neurodegenerative disorders in a mammal is provided. The cell system includes a population of neurons differentiated from umbilical mesenchymal stem cells for expressing at least one of tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), glutamate decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC) and dopaminergic transporter (DAT) in a cell culture. A method for treating neurodegenerative disorders in a mammal is also provided. The method comprises the steps of differentiating umbilical mesenchymal stem cells into a population of neurons that express at least one of TH, DBH, GAD, AADC and DAT in a cell culture, and transplanting the population of neurons into the brain of the mammal.

L-DOPA amide derivatives, pharmaceutical compositions containing same and their use in the treatment of conditions associated with impaired dopaminergic activity/signaling (e.g., Parkinson disease) are disclosed.

Polynucleotide molecules and the proteins encoded by the molecules, diagnostic and treatment methods for neurological disorders characterized by protein aggregation are provided. Genes are described herein that affect the misfolding of, and subsequent aggregation of, aggregation-prone proteins such as alpha-synuclein and have implications for the diagnosis and treatment of neurological diseases related to protein aggregation such as Parkinson's disease. Knockdown of expression of the genes described herein using RNAi results in alpha-synuclein protein aggregation in a C. elegans model of protein aggregation. Dopaminergic neuroprotection after exposure to the neurotoxin 6-OHDA or overexpression of alpha-synuclein may also be provided by overexpression of proteins. Knowledge of genes relating to protein misfolding and aggregation provides powerful means to develop diagnostic screening methods, mutation analysis and drug design information for the development of novel therapeutic and neuroprotective compounds to treat neurodegenerative diseases such as Parkinson's disease.

Pharmaceutical formulations for treating neurological diseases are described, wherein the formulations comprise a pharmaceutically active agent-transport moiety complex. The formulations are suitable for administration via an intranasal route. Neurological diseases and conditions are associated with reduced brain insulin signaling (i.e., CNS insulin insensitivity), reduced dopaminergic signaling, reduced serotonergic signaling, reduced cholinergic signaling, or reduced GABAergic signaling, and include Alzheimer's disease, Parkinson's disease, epilepsy, neuropathic pain, fibromyalgia, post-herpetic neuralgia, insomnia, or anxiety. Neurological diseases also include cancers of the central nervous system (CNS).

The present invention discloses an application of flavone compound or its derivative in preparation of medicine for curing psychic disease and nervous disease. Said invention also discloses a medicine composition containing flavone compound or its derivative. Said invention also provides an excitant of dopamine transport protein firstly, and the tests show that the dopamine transport protein can be excited.

Hydrophilic transportable N-linked glycosyl dopaminergic prodrug compounds according to FORMULA V and methods of their use,

wherein, Ring 1 comprises an aryl or heteroaryl ring having 4 to 8 carbon atoms, among which atoms are counted “X” and “Y”;

• • each of X and Y is optional; X, when present is either —C(R₁)₂— or —C(R₁)₂—; Y, when present, is either —CH₂— or —CH₂—CH₂—;
  • z, R₅ and R_5′. are optional, and when present z, R₅ and R_5′ together form a lower alkyl or a substituted lower alkyl moiety; N is part of either an amine or an amide linkage; E is a saccharide which forms a linkage with N through a single bond from a carbon or oxygen atom thereof;
  • R₁ and R₄ are selected form the group consisting of hydrogen, hydroxyl, halogen, halo-lower alkyl, alkoxyl, alkoxyl-lower alkyl, halo-alkoxy, thioamido, amidosulfonyl, alkoxylcarbonyl, carboxamide, aminocarbonyl, and alkylamino-carbonyl;
  • R₂ and R₃ are hydroxyl;
  • R₅ and R₆, when present, are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carbonyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialkylamino-carbonyl; and,
  • R₆ and R_6′ are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carboxyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialylamino-carbonyl, with the proviso that Ring 1 is capable of binding to any of: a dopaminergic receptor selected from the group consisting of a D1 receptor and a D5 receptor; a DAT transporter; a VMAT transporter; and, with the proviso that E is capable of binding to a GLUT transporter selected from the group consisting of a GLUT1 receptor and a GLUT3 receptor.

Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (C_max) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

The present invention relates to novel methods and compositions for gene therapy. The invention also provides methods for treating diseases or disorders of the central nervous system associated with dopaminergic hypoactivity, disease, injury or chemical lesioning, including Parkinson's disease, manic depression, and schizophrenia.

The present invention relates to a method for regulating the differentiation of neural stem cells or neural progenitor cells into dopaminergic neural cells, the method comprising increasing or inhibiting the activity of ADAM17 and/or ADAM10 in neural stem cells or neural progenitor cells, and to the use of an activator or inhibitor of ADMA17 and/or ADAM10.

The method and composition according to the invention can regulate the activity of ADAM17 and/or ADAM10 in neural stem cells or neural progenitor cells to increase dopaminergic neural cells in the midbrain area, and thereby providing the effect of treating diseases induced by the death of dopaminergic neural cells such as Parkinson's disease. In addition, the method and composition according to the invention can inhibit the activity of ADAM17 and/or ADAM10, and thereby improving effect of treating diseases such as tumor. Thus, the present invention is very useful.

The present invention provides a novel proteinaceous composition that increases the levels of dopamine (DA) in neurons. Therefore, provided are methods for treating conditions caused by the deficiency of dopamine and/or by the loss of DA neurons or injury to DA neurons. An example includes Parkinson's disease. Also provided are methods for isolating and partially purifying the proteins and further characterizing the same.

Provided is a method for the derivation of neural stem cells (NSCs) from embryonic stem cells (ESCs) and the use of the NSCs for treatment of various neural disorders. The NSCs that are derived from the ESCs are tissue-specific multipotent NSCs with a stable growth rate, unlimited self-renewal capacity, and a predictable differentiation profile. Being both non-tumorigenic and engraftable, the NSCs of the present invention have utility in repopulation stroke-damaged tissue. The NSCs of the present invention may be differentiated to produce tyrosine-hydroxylase expressing neurons, which may be used as a source of dopaminergic neurons for subjects suffering from a condition characterized by dopaminergic dysfunction, such as Parkinson's disease.

The present invention provides methods for: (i) treating and/or preventing Parkinson's disease in a subject without causing cognitive impairment by using dopamine replacement gene therapy to maintain or restore constant physiological dopaminergic tone in both the dorsal and ventral striatum of the subject; (ii) normalising neuronal electrical activity in basal ganglia and/or subthalamic nucleus in a Parkinson's disease subject; and (iii) treating and/or preventing dyskinesias associated with oral L-dopa administration in a Parkinson's disease subject by administration of a vector system for dopamine replacement gene therapy to the subject.

Bromocriptine citrate administered to a vertebrate, animal or human, can be used for any purpose including, e.g., the long-term modification and regulation of metabolic disorders, including prediabetes, obesity, insulin resistance, hyperinsulinemia, hyperglycemia and type 2 diabetes mellitus (T2DM) and/or, e.g., the treatment of other medical disorder(s) including immune or endocrine disorders or diseases. Bromocriptine citrate is administered over a limited or extended period at a time of day dependent on re-establishing the normal circadian rhythm of central dopaminergic activity of healthy members of a similar species and sex. Insulin resistance, hyperinsulinemia and hyperglycemia, T2DM, prediabetes, MS or all, can be controlled in humans on a long term basis by such treatment inasmuch as the daily administration of bromocriptine citrate resets neuronal activity timing in the neural centers of the brain to produce long term effects.

The invention discloses a method for inducing umbilical cord mesenchymal stem cells to be differentiated into dopaminergic neurons. According to the method, a two-step combination method of pre-induction and induction is adopted, optimized pre-induction culture solution and induction culture solution are prepared, and a glycoside compound improved in structure is added as an inducer, so that the umbilical cord mesenchymal stem cells are successfully induced to be differentiated into the dopaminergic neurons and the differentiation ratio is relatively high.

A human embryonal stem cell, neural stem cell, neural precursor cell, neural cell or dopaminergic neuron is genetically modified to overexpress at least one of certain genes identified as regulated in the developing human ventral mesencephalon, and more particularly, up-regulated in the ventral tegmentum. The genes are associated with dopaminergic differentiation.

The invention relates to the field of stem cell biology, in particular to midbrain dopaminergic neural precursor cells and a preparation method and application thereof. The midbrain dopaminergic neural precursor cell expresses Lmx1a+, Foxa2+, En1+ and Otx2+, wherein the midbrain dopaminergic neural precursor cell does not express one or more of Nkx2.1, DBX1 and GBX2. The method for preparing the mesencephalic dopaminergic neural precursor cell comprises the following steps: embryoid bodies are formed, midbrain floor cells are obtained, and midbrain dopaminergic neural precursor cells are obtained. By adopting the preparation method, the mesencephalic dopaminergic nerve cells can be rapidly and efficiently differentiated from the human pluripotent stem cells, and the problems are solved that an existing differentiation method is long in time, unstable in effect and low in efficiency, the culture system containing serum or the trophoblast cells are not conducive to the production of subsequent clinical-grade cell preparations and the like.

It is shown here that hedgehog proteins possess novel activities beyond phenotype specification. Using cultures derived from the embryonic day 14.5 (E14.5) rat ventral mesencephalon, we show that hedgehog is also trophic for dopaminergic neurons. Interestingly, hedgehog not only promotes dopaminergic neuron survival, but also promotes the survival of midbrain GABA-immunoreactive (GABA-ir) neurons.