305 results about "Neurotrophic factors" patented technology

Methods and devices are disclosed for the non-invasive treatment of neurodegenerative diseases through delivery of energy to target nervous tissue, particularly the vagus nerve. The devices include a magnetic stimulator having coils with toroidal windings, which are in contact with an electrically conducting medium that is adapted to conform to the contour of a target body surface of a patient. The coils induce an electric current and / or an electric field within the patient, thereby stimulating nerve fibers within the patient. The stimulation brings about reduction of neuroinflammation in patients suffering from conditions comprising Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis, postoperative cognitive dysfunction and postoperative delirium. Reduction in inflammation is effected by enhancing the anti-inflammatory competence of cytokines such as TGF-beta, wherein a retinoid or components of the retinoic acid signaling system provide an anti-inflammatory bias, by enhancing anti-inflammatory activity of a neurotrophic factor such as NGF, GDNF, BDNF, or MANF, and / or by inhibiting the activity of pro-inflammatory cytokines such as TNF-alpha.

A nutritional supplement composition for normalizing impaired or deteriorating neurological function in humans is composed of: at least one agent which promotes synthesis of ATP and / or creatine phosphate in the body, at least one antioxidant for scavenging free radicals in at least one pathway in the body; at least one agent for normalizing or maintaining membrane function and structure in the body; at least one agent for normalizing or maintaining normal neurotransmitter function in the body; at least one agent for down-regulating cortisol action; and at least one agent for suppressing activation of apoptotic pathways in the body. The composition may further contain one or more of: at least one agent for suppressing inflammation in the body; at least one agent for normalizing or maintaining vascular wall function and structure in the body; at least one agent for normalizing or maintaining function of nerve growth factors and / or neurotropic factors in the body; at least one agent for suppressing toxic metal ionic effects; at least one agent for normalizing or maintaining methyl metabolism in the body; at least one agent for normalizing or maintaining metabolism of insulin and glucose in the body; and at least one agent for up-regulating activity of heat shock proteins in the body. A method for normalizing impaired neurological function in humans modulating nutrient partitioning in a human involves administering the aforementioned composition to the human, preferably on a daily basis, for a therapeutically effective period of time. Preferably, the method further involves having the human follow a stress reduction program, and / or a cognitive retraining program, and / or a dietary program designed to maximize insulin and glucose metabolism.

A tissue-engineered peripheral nerve for reparing the demaged peripheral nerve is composed of neural canal and neuroglia cells or stem cells, and is prepared through preparing neural canal, preparing neurotrophic factor release controllable microspheres, and configuring the tissue-engineered peripheral nerve.

Disclosed are methods and compositions for maintaining neural pathways in a mammal including: enhancing survival of neurons at risk of dying; inducing cellular repair of damaged neurons and neural pathways; stimulating neurons to maintain their differentiated phenotype; and promoting dendritic outgrowth, including maintaining dendritic arbors and regenerating dendritic architecture. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration. In another embodiment, the invention provides methods and compositions which include a morphogen or morphogen-stimulating agent, and a nerve trophic factor or nerve trophic factor-stimulating agent at concentrations effective for stimulating dendrite outgrowth. The morphogen and the nerve trophic factor can be admixed in combination.

A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process.

A method of treating brain disorders involving loss of cells that respond to GDNF is disclosed. In one embodiment, the invention comprises the steps of (a) transducing human neural stem cells with glial-derived neurotrophic factor (GDNF), wherein the GDNF gene is under control of an inducible promoter system, and (b) transplanting the transduced cells into the brain of a patient.

The invention discloses a nerve duct and a preparation method as well as use thereof. The nerve duct is composed of 'shell-core' structured nanofiber, a core layer of the 'shell-core' structured nanofiber contains a biological active component, and a shell layer of the 'shell-core' structured nanofiber contains a biodegradable material; the inside diameter of the nerve duct is 0.5-5.0mm, and the outside diameter thereof is 1.0-6.0mm; the biological active component is a neurotrophic factor; and the biodegradable material is selected from one or more than one of the following components: polylactic-co-glycolic acid (PLGA), poly(lactic acid-caprolactone copolymer) (P (LLA-CL)) and poly(3-hydroxybutyrate) (PHB) or polyphosphoester (PPE).

The invention provides novel combination therapies for treating neurodegenerative disease which comprise a) neurotrophic factors or suitable fragments thereof and b) agents capable of causing inhibition of a gene responsible for the neurodegenerative disease. The invention provides novel nucleic acid sequences, methods, and systems suitable for applications of these combination therapies.

A neurotrophic factor production promoting device is provided, which is able to promote production of a neurotrophic factor or neurotrophic factor-like substance in an affected area by a simple technique that, regardless of the place of treatment, can be performed without transplantation of cells or injection into the affected area, in order to prevent or treat various diseases such as brain diseases. In order to apply a high frequency alternating magnetic field in the range of 20 MHz to 180 MHz, 280 MHz to 600 MHz, or 700 MHz to 1000 MHz to cells at a magnetic flux density of no more than 0.01 Tesla, the neurotrophic factor production promoting device includes a high frequency electromagnetic wave generating means generating a high frequency electromagnetic wave of the abovementioned frequency, in which the magnetic stimulation by the high frequency alternating electromagnetic field of the abovementioned high frequency allows the intracellular concentration of calcium ions to be increased so that exocytosis of the neurotrophic factor group is induced, and the magnetic stimulation allows messenger ribonucleic acid (mRNA) of the neurotrophic factor group to be increased in the cells so that the synthesis and extracellular release of the neurotrophic factor group are promoted.

The present invention is directed to the compositions and methods of preparing hydrogel-grafted nerve guides for peripheral nerve regeneration. Particularly, the present invention describes the nerve guides and methods for preparation of hydrogel-grafted nerve guides with encapsulated neurotrophic factors and a nanofiber mesh lining the inner surface of the guide. The present invention also provides methods for peripheral nerve repair using these hydrogel-grafted nerve guides.

The invention discloses lactobacillus plantarum DP189 and application thereof, and relates to the field of functional food microorganisms. The strain is preserved in China Center for Type Culture Collection on March 25 , 2019 with the preservation number of CCTCC NO:M2019199. By means of the strain, the learning and memory capability of a depressed rat can be improved; the level of brain-derived neurotrophic factors of the depressed rat can be improved; the injury to hippocampal neurons and apoptosis of neuron cells of the depressed rat are reduced; the content of apoptosis proteins JUK2 and Bcl-2 of brain tissue of the depressed rat is lowered; the abundance of verrucomicrobiaceae of the intestinal tract is lowered; the abundance of bacterium lacticum of the intestinal tract is improved, the alpha-diversity of the intestinal floras is improved, and the intestinal flora disturbance of the depressed rat is alleviated. In this way, the lactobacillus plantarum DP189 has good effects of preventing and treating depression / anxiety, infantile autism and inflammatory enteritis. The strain has the anti-depression function, and can serve as a functional probiotic bacterium for preventingand treating the depression, infantile autism and inflammatory enteritis, and a new idea is provided for clinical intervention with and control over depression and other relevant mental diseases.

The invention discloses a chitosan artificial nerve graft containing a neurotrophic factor and a preparation method thereof. In the chitosan artificial nerve graft, chitosan is processed into a nerve conduit with a porous structure and high tensile strength by performing processes such as weak acid dissolving, injection molding, molding, neutralization fixing, cleaning, freeze drying and the like under the condition of not adding any foaming agent or crosslinking agent. The nerve conduit contains cells or tissues which have treating effects and are included or distributed inside or on the surfaces of tubular body pores, including autologous bone marrow stem cells, autologous bone mesenchymal stem cells, schwann cells or dorsal root ganglion tissues or combinations thereof. A tissue engineering nerve can be used for repairing peripheral nerve defect and can be applied to repairing of spinal cord injury simultaneously.

The invention relates to polypyrrole biological conductive hydrogel, as well as a preparation method and application thereof. The preparation method comprises the following steps; preparing carboxymethylchitosan hydrogel from carboxymethyl chitosan by using a crosslinking agent under a certain condition, and performing freeze-drying treatment; performing electrochemical synthesis on a pyrrole monomer to obtain polypyrrole, adding a dopant into the polypyrrole to perform modification and performing ball-milling and crushing to enable the particle size to be matched with the pore diameter of pores of the carboxymethylchitosan hydrogel; blending nerve growth factors into water, adding modified polypyrrole particles, stirring and dispersing uniformly, putting the carboxymethylchitosan hydrogel to enable the solution to be completely absorbed, adding water, vibrating, and completely swelling and balancing to obtain the polypyrrole biological conductive hydrogel. When the polypyrrole biological conductive hydrogel is applied to neural restoration, sustained release of neurotrophic factors can be completed, nerve cells can be subjected to certain electrical stimulation through bioelectrical or external electrical stimulation, proliferation and differentiation of the nerve cells are promoted through double effects of electric stimulation and neurotrophic factor induction, and nerve axon growth is guided.

The present invention provides methods of promoting the revascularization and / or reenervation of central nervous system lesions using an in-situ crosslinkable hydrogel. The present invention also provides methods of treating a spinal cord injury by topically delivering to the spinal cord injury site a vehicle comprising a neurotrophic factor and / or anti-inflammatory agent. Also provided are methods of treating a spinal cord injury by topically administering or delivering a hydrogel to the injury site.

The present invention relates to glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophin that exhibits a broad spectrum of biological activities on a variety of cell types from both the central and peripheral nervous systems. The present invention involves the cloning and characterization of receptors for GDNF. Nucleic acid and amino acid sequences are described for GDNFR protein products. A hydrophobic domain with the features of a signal peptide is found at the amino terminus, while a second hydrophobic domain at the carboxy terminus is involved in the linkage of the receptor to the cell membrane. The lack of a transmembrane domain and cytoplasmic region indicates that GDNFR requires one or more accessory molecules in order to mediate transmembrane signaling. GDNFR mRNA is widely distributed in both nervous system and non-neural tissues, consistent with the similar distribution found for GDNF.

The invention aims to provide a neural restoration material combined with the acellular nerve application. The neural restoration material is prepared from nerves of an acellular allogene or acellular heterogeneous living organism, a restoration material, a microtubulin inhibitor, neurotrophic factors and stem cells. The neural restoration material disclosed by the invention has good biocompatibility, can provide nutrition supplies needed by nerve regeneration and restoration, is capable of maintaining an optimal physicochemical and biology microenvironment for nerve regeneration for a long time and has dual functions of preventing nerve tumor formation and promoting defect nerve restoration.

The present invention relates to a method for treating a behavior disorder comprising the administration of a therapeutically effective amount of antihistamine, such as ceterizine, fexofenadine; loratadine, and desloratadine. The behavioral disorders may include ADHD, anxieity, depression, and autism. The method may include the administration of the antihistamine in combination with a stimulant medication, such as methylphenidate, thereby to achieve a synergistic effect. In any event, the amount of antihistamine and / or stimulant is effective to downregulate neurotrophic factors such as nerve growth factor or CD40. The invention is also directed to a method of preventing the onset of behavior disorders in patients presenting with symptoms of allergic rhinitis.

The invention discloses an expression structure method for constructing Glial cell line-Derived Neurotrophic Factor (GDNF) fusing penetrating peptides, the purification of an expressed protein product and the significance thereof, which is mainly characterized in that (1) GDNF parent is a human source mature type; (2) the N-tail end of the GDNF is fused with PEP-1 penetrating peptides comprising the 21 amino acid; and the expression product of the constructed penetrating peptides GDNF fusing the gene expression plasmid has the membrane penetrating function and biological function of GDNF and can be clinically applied in the treatment of the related diseases.

The invention relates to a bioengineering technology, in particular to a small-caliber biotic artificial blood vessel with anti-thrombus formation and anti-intimal hyperplasia functions. Firstly, the key technology of accellular materials and natural polymer composition is used, and through multiple modes, neurotrophic factors are effectively coupled as functional modules to perform modification on blood vessel supports. Furthermore, through the strategy of constructing in body, the small-caliber engineering blood vessel modified by the neurotrophic factors is transplanted in body, the scour and the pressure of hemodynamics are overcome in body, endothelial progenitor cells in circulation are captured initiatively, the endothelial progenitor cells are further induced to differentiate into endothelial cells in situ, and the progress and the quality of endothelialization of blood vessel graft are speeded. Meanwhile, the generation of blood capillaries is promoted and nurtured, the blood vessel implants are promoted to remodel in body, therefore, the effects of anti-thrombus formation and anti-intimal hyperplasia can be effectively achieved, and the patency rate after the small-caliber biotic artificial blood vessel is transplanted is increased. Active small-caliber tissue engineering blood vessels used for coronary arterie bypass grafting, hematodialysis and cerebrovascular replacement in clinic are built.

The present invention generally relates to the field of treatment of neuronal disorders and more particularly to neurotrophic factor MANF and uses thereof. The present invention provides a pharmaceutical compound comprising MANF nucleic acid molecule, MANF protein or a functional fragment thereof for the treatment of a peripherial neuropathy including Alzheimer's disease, Parkinson's disease, epilepsy, drug addiction and ischemic brain injury.

An application of a phthalide compound in preparing a medicament. The medicament is specially used for promoting a stem cell to secrete one of the following items: telomerase, a neurotrophic factor (brain-derived neurotrophic factor, BDNF), a stem cell chemotactic factor (stromal cell-derived factor-1, SDF1), a stem cell chemotactic factor receptor (CXC chemokine receptor 4, CXCR4), and an immunoregulatory factor; a kit comprising a phthalide compound and a stem cell is also provided.

Leptin resistance ameliorating agents comprising as the active ingredient a neurotrophic factor such as BDNF or a trk receptor ligand, namely, agents for ameliorating, treating or preventing hypertension, sterility, obesity, glucose metabolic disorders, ischemic diseases, growth hormone secretion insufficiency, growth hormone hyposecretion, immune function disorder, etc. caused by leptin resistance.

This invention relates to compounds, pharmaceutical compositions and methods for use in the prevention and treatment of cerebral insufficiency, including enhancement of receptor functioning in synapses in brain networks responsible for basic and higher order behaviors. These brain networks, which are involved in regulation of breathing, and cognitive abilities related to memory impairment, such as is observed in a variety of dementias, in imbalances in neuronal activity between different brain regions, as is suggested in disorders such as Parkinson's disease, schizophrenia, respiratory depression, sleep apneas, attention deficit hyperactivity disorder and affective or mood disorders, and in disorders wherein a deficiency in neurotrophic factors is implicated, as well as in disorders of respiration such as overdose of an alcohol, an opiate, an opioid, a barbiturate, an anesthetic, or a nerve toxin, or where the respiratory depression results form a medical condition such as central sleep apnea, stroke-induced central sleep apnea, obstructive sleep apnea, congenital hypoventilation syndrome, obesity hypoventilation syndrome, sudden infant death syndrome, Rett syndrome, spinal cord injury, traumatic brain injury, Cheney-Stokes respiration, Ondines curse, Prader-Willi's syndrome and drowning. In a particular aspect, the invention relates to compounds useful for treatment of such conditions, and methods of using these compounds for such treatment.

The invention discloses a preparation technology of a novel nerve conduit, and belongs to the technical field of tents of biological tissue engineering. The preparation technology sequentially comprises a preparation technology of GDNF (glial-derived neurotrophic factor)-carried gelatin microspheres, a synthesizing technology of gelatin-methacrylamide hydrogel, a preparation method of polycaprolactone / gelatin electricity texture nerve conduits, and a combining method of the electricity texture nerve conduits and the GDNF-carried gelatin microspheres. The preparation technology has the advantages that a tent structure with good degradability, biological compatibility and biological safety is realized, and the GDNF is controlled and released by the GDNF-carried gelatin microspheres; compared with blank groups and collagen conduit groups, the regeneration of peripheral nerves is effectively promoted, and the structure and function of restoring damaged nerves can reach the effect similar to the effect of autotransplantation groups; the defect nerves can be bridged, and the stability of axon regeneration environment can be maintained; the invasion of peripheral connective tissues is prevented; the saturing of near and far-heart breaking ends of smaller nerve defect is solved, and the restoration of larger nerve defect is solved.

OP / BMP morphogen is combined with GDNF / NGF neurotrophic factors in promoting the survival or growth, or inhibiting the death or degeneration, of mammalian cells, particularly neural cells, which express OP / BMP-activated serine / threonine kinase receptors and GDNF / NGF-activated tyrosine kinase receptors. Also discosed are methods for the treatment of such cells, including treatments for mammals afflicted with, or at imminent risk of, damage or injury to, such cells, as well as new pharmaceutical preparations for such treatments.

The invention discloses a GDNF-carrying microbubble preparation and a method for making the same. The GDNF-carrying microbubble is composed of a lipid bilayer internally wrapping biological inert gas and biotinylated GDNF connected to the outside of the lipid bilayer. Employing MRI real-time guided low-frequency focused ultrasound combined with BBB opening by the GDNF-carrying microbubble to irradiate a craniocerebral parietal cortex area of a rat (the optimal parameters are set to be: probe frequency 1 Hz, microbubble 0.5 mL, irradiation period 60 s, sound pressure 0.8 MPa, and time-delay 60s) can promote GDNF to penetrate the BBB and increase the effective drug concentration of GDNF in the central nervous system. The pharmacological research after effective macromolecule breaking through of BBB by low-frequency focused ultrasound combined with target microbubble technique will further increase the advantage of neurotrophic factors in treatment of brain diseases and provide the scientific evidence for GDNF to treat nervous centralis diseases.

A method of treatment of neurodegenerative diseases using neuronal cell transplants is provided. The growth, survival and integration of the transplanted neuronal cells is enhanced by a method of culturing the neuronal cells with drugs having an affinity for immunophilins. Immunophilin binding drugs are optionally administered to the patient during transplantation and / or post-operatively. Neurotrophic factors can also be administered to the neuronal cells in vitro, or to the patient during the transplantation procedure and / or post-operatively.