313 results about "Primary motor neuron" patented technology

The invention relates the method of treatment or amelioration of mitochondrial disorders such as Alzheimer's disease, Parkinson's disease, Friedreich's ataxia (FRDA), cerebellar ataxias, Leber's hereditary optic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Myoclonic Epilepsy with Ragged Red Fibers (MERFF), amyotrophic lateral sclerosis (ALS), motor neuron diseases, Huntington's disease, macular degeneration, and epilepsy, with chroman derivatives of Formula I or Formula II as described herein.

The present invention relates generally to efficient delivery of viral vectors to cells of the CNS, particularly useful in the treatment of neurodegenerative disorders and motor neuron diseases. The invention involves selecting a first population and a second population of synaptically connected neurons, wherein a therapeutic polypeptide is to be expressed in said second population of neurons; and administering rAAV virions comprising a therapeutic gene to said first subpopulation of neurons of said subject such that the rAAV virions are transported across a synapse between synaptically connected neurons. In another aspect the present invention also comprises the use of rAAV virions carrying a transgene in the preparation of a medicament for the treatment of a disease in a subject, wherein a first population and a second population of synaptically connected neurons are selected and a therapeutic polypeptide is to be expressed in said second population of neurons; and a medicament comprising recombinant adeno-associated virus (rAAV) virions is delivered to said first population of neurons of the subject, wherein said virions comprise a nucleic acid sequence that is expressible in transduced cells to provide a therapeutic effect in the subject, and wherein said rAAV virions are capable of transducing a synaptically connected neurons.

The present invention relates to compositions and methods for the delivery of therapeutic proteins to the CNS using recombinant AAV vectors. More specifically, the invention relates to compositions and methods for delivering proteins into the cerebrospinal fluid of mammalian subjects through peripheral administration of AAV vectors. The invention may be used to treat various disorders of the central nervous system, including degenerative diseases and motor neuron diseases.

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.

Methods and systems for the treatment for ALS incorporating stem cells harvested from the subject to be treated. These stem cells may be genetically altered with the addition of several genes of interest. Then, the patient will receive systemic gene therapy for the muscles and directed specifically at motor neurons. In this multi-pronged treatment approach, the stem cells provide immune regulation and the regeneration of motor neurons. And, the new motor neurons carry the added genes, which are protective against motor neuron death from ALS. The systemic therapy increases the amount of genes, which further reduces the effects of ALS. Additional gene therapy administered in the muscle will be further protective of the axon, while maintaining muscle mass and function.

The invention relates to a CPG (Certified Program Generator) feedback control method of biomimetic robot fish movement, comprising the following steps of: providing a CPG feedback control model for receiving feedback signals by using different parts of a high-level control module, a CPG, a motor neuron, and the like; receiving biomimetic robot fish body state information and water environment information by the high-level control module; transmitting a corresponding command by treating the information and making a decision; and selecting a corresponding movement moulding plate to determine a suitable CPG configuration, wherein the suitable CPG configuration is used for controlling the parts of the biomimetic robot fish body to carry out rhythmic movement and non-rhythmic movement. The invention provides a reference for the feedback control theoretical design of the biomimetic robot fish movement and can realize mobile, flexible and independent autokinetic movement.

This invention provides a new technology for management of back pain by stimulating the spinal cord in a manner that renders it refractory to transmission of deleterious or undesirable sensory input. The electrical stimulus comprises high frequency pulses in a regular or complex pattern or that are stochastically produced under microprocessor control. The stimulus is applied directly to the surface of the spinal cord from within the spinal canal, which provides important benefits over previous technology. The stimulus alleviates symptoms and signs of back pain, while minimizing the risk of side effects such as paresthesia, and potentially minimizing the effects on motor neuron transmission and proprioception.

Disclosed are methods for generating a neuron expressing Hoxc8 transcription factor or a caudal motor neuron comprising culturing an embryonic stem cell in a composition which is essentially free of retinoids and comprises an isotonic salt solution, so as to generate the neuron which expresses Hoxc8 transcription factor or the caudal motor neuron. Disclosed are also methods for generating a caudal brachial motor neuron, a thoracic motor neuron, or a lumbar motor neuron from an embryonic stem cell in a composition essentially free of retinoids and comprising ADFNK medium, an amount of FGF-2, or Gdf11 respectively. Disclosed are also methods of transplanting a motor neuron into a subject comprising generating the motor neuron and transplanting the motor neuron into the subject. Disclosed is also a population of motor neuron cells enriched for motor neuron cells expressing Foxp1 and expressing a gene associated with Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS).

A method of targeting therapeutic molecules to motor neurons is disclosed. In one embodiment, this method comprises the steps of (a) synthesizing a prodrug comprising a therapeutic molecule covalently bound to a polymeric delivery vehicle, and (b) conjugating the prodrug to a botulinum neurotoxin heavy chain.

The invention relates the method of treatment or amelioration of mitochondrial disorders such as Alzheimer's disease, Parkinson's disease, Friedreich's ataxia (FRDA), cerebellar ataxias, Leber's hereditary optic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Myoclonic Epilepsy with Ragged Red Fibers (MERFF), amyotrophic lateral sclerosis (ALS), motor neuron diseases, Huntington's disease, macular degeneration, and epilepsy, with chroman derivatives of Formula I or Formula II as described herein.

Formulations and methods of use thereof for restoring neuronal, muscular (cardiac and striated) and / or retinal tissue function in children and adults afflicted with chronic neurodegenerative diseases, such as neurodegenerative movement disorders and ataxias, seizure disorders, motor neuron diseases, and inflammatory demyelinating disorders, are described herein. Examples of disorders include Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). The method involves administering a pharmaceutical composition containing an effective amount of a tetrahydrobenzathiazole, preferably a formulation consisting substantially of the R(+) enantiomer of pramipexole. R(+) pramipexole is generally administered in doses ranging from 0.1-300 mg / kg / daily, preferably 0.5-50 mg / kg / daily, and most preferably 1-10 mg / kg / daily for oral administration. Daily total doses administered orally are typically between 10 mg and 500 mg. Alternatively, R(+) pramipexole can be administered parenterally to humans with acute brain injury in single doses between 10 mg and 100 mg and / or by continuous intravenous infusions between 10 mg / day and 500 mg / day.

Compounds of formula:and pharmaceutically acceptable salts, esters and solvates thereof, where variables are defined in the specification, useful generally as inhibitors of protein kinases and particularly useful for inhibition of GSK-3.Pharmaceutically compositions and medicaments containing a compound of the invention are provided. The invention provides methods of treatment of protein kinase-related disease, disorders or conditions. The invention provides methods of treatment of GSK-3-related diseases, disorders or conditions. More specifically, methods of treatment of bipolar disorder, including mania, schizophrenia, stroke, epilepsy, motor neuron disease, cranial or spinal trauma, neurodegenerative disorders, including multiple sclerosis (MS), Alzheimer's disease, Fragile X syndrome, autism, Huntington's disease, Parkinson's disease, amylotrophic lateral sclerosis (ALS), AIDS-associated dementia, diabetes, particularly type II diabetes, cardiomycete hypertrophy, reperfusion / ischemia, cancer, particularly colorectal cancer, pancreatic cancer, allergies and / or asthma and hair loss or baldness.

The invention which relates to the medicinal field discloses an application of butylphthalide and derivatives thereof in the preparation of medicines for preventing and treating ALS (amyotrophic lateral sclerosis). Butylphthalide and the derivatives, which can delay the disease time of an SOD1-G93A transgenic mouse, prolong the lifetime of the mouse, reduce the degenerative change of spinal motorneurons, obviously increase the survival number of spinal anterior horn motor neurons of the mouse, reduce the electrophysiological abnormality of the transgenic mouse, obviously improve the action potential amplitude and the motion unit number of compound muscles, substantially inhibit the activation of astrocytes and microglial cells in the spinal cord of the mouse, and obviously reduce the expression level of iNOS and NF-kappaBp65, have good application prospects in the prevention and the treatment of the ALS.

The present invention is concerned with functional electrical stimulation (FES) of paraplegics having spinal cord injuries (SCI), especially for the purpose of walking, where stimulation is applied to motor neurons below the level of the SCI. Specifically, the invention is concerned with FES in closed-loop where closed loop operation is provided by wireless feedback by EMG signals recorded via noninvasive surface EMG electrodes. No wire connections are required between the EMG electrodes and a signal processor (SP) for providing the feedback signal to the SP. Also, no wire feedback is required to send timing information from the stimulation signal generator to blocking circuits, in cases where such circuits are required to protect the wireless transmitters of the feedback information from being damaged by the stimulation pulses. Wireless operation is facilitated by miniature chips (receivers and transmitters), such as used in the Bluetooth technology. Hence, the paraplegic users are not burdened with any wires that are otherwise needed for closed-loop operation and with the need to connect them between the patient's back, legs, and a pocket-borne control box. Furthermore, closed loop operation frees the patients from the need to manually adjust stimulation levels with progression of muscle fatigue.The present invention allows the achieving closed-loop FES without requiring the sharing the same electrode for both stimulation and EMG recording and which requires complex control and non-standard electrodes. The avoidance of electrode-sharing further allows using regular and widely available stimulation electrodes and regular surface EMG electrodes, such as described in Graupe and Kohn: “Functional Electrical Stimulation for Ambulation by Paraplegics”, 1994.In certain realizations of the present invention, the blocking circuit discussed above requires no input from the stimulus signal generator, while such inputs are essential in any electrode-sharing design since pulse level is highest at the stimulation site. Hence, also no wireless receiver is required next to the EMG electrodes and no wireless transmitter is required next to the stimulus signal generator.In certain other realizations, blocking circuits are not required at all.

Methods for expanding proliferating populations of neuronal subtype-specific progenitors are provided herein. In particular, the present invention provides methods for maintaining the unique gene profile and differentiation potential of neuronal subtype-specific progenitors, such as motor neuron progenitors and hindbrain serotonergic neural progenitors.

The invention is directed to methods of preventing, delaying, or reducing motor neuron damage in an individual by administering to the individual a composition containing an extract of gingko biloba. The methods can be used to treat an individual having or at risk of having a condition characterized by motor neuron damage, e.g., amyotrophic lateral sclerosis. The invention also includes methods of preventing or reducing weight loss in an individual by administering to the individual a composition containing an extract of gingko biloba.

A composition comprising a molecule for use in the delivery of the molecule to the peripheral nervous system (PNS) and / or to the central nervous system (CNS), wherein the composition is administered by regional infusion.

Formulations and methods of use thereof for restoring neuronal tissue function in children and adults afflicted with chronic neurodegenerative diseases, such as neurodegenerative movement disorders and ataxias, seizure disorders, motor neuron diseases, and inflammatory demyelinating disorders. Examples of disorders include Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). The method involves administering a pharmaceutical composition containing an effective amount of a tetrahydrobenzathiazole, preferably a formulation consisting substantially of the R(+) enantiomer of pramipexole. R(+) pramipexole is generally administered in doses ranging from 0.1-300 mg / kg / daily, preferably 0.5-50 mg / kg / daily, and most preferably 1-10 mg / kg / daily for oral administration. Daily total doses administered orally are typically between 10 mg and 500 mg. Alternatively, R(+) pramipexole can be administered parenterally to humans with acute brain injury in single doses between 10 mg and 100 mg, and / or by continuous intravenous infusions between 10 mg / day and 500 mg / day.

A composition for treating, ameliorating and / or preventing conditions associated with cognitive decline and / or motor neuron death comprise a fatty acid component enriched for one or more activated fatty acids and a nutraceutically acceptable excipient. A method for treating, ameliorating and / or preventing conditions associated with cognitive decline and / or motor neuron death includes administering a fatty acid component enriched for one or more activated fatty acids.

Methods of treating pain are disclosed, wherein a non-pulsed, low-frequency electrical current is applied to the nerve carrying the pain signals in order to suppress transmission of those signals. In desired embodiments, the current is applied in a direction transverse to the nerve axis. Such currents have been found not to induce motor-neuron recruitment, meaning these methods can treat pain without causing muscle spasm or other muscular responses. A cuff for applying such a current transverse to the nerve axis is also disclosed.

A neural stem cell preparation for treating human myelopathy, especially the motor neuron diseases, is prepared through digesting the brain tissue of human embryo, adding to culture medium, centrifugal processing, mechanical beating to obtain cell suspension, culturing in culture medium in CO2 atmosphere, screening neural stem cell balls, and passage by 3-6 generations.

A method of generating neural stem cells or motor neurons is disclosed, the method comprising up-regulating a level of at least one exogenous miRNA and / or down-regulating at least one miRNA using an agent which hybridizes to the miRNA in mesenchymal stem cells (MSCs) or down-regulating Related to testis-specific, vespid and pathogenesis protein 1 (RTVP-1).

An object of the present invention is to provide a novel medicament with which motor neuron diseases can be treated. According to the present invention, there is provided a therapeutic agent for motor neuron diseases which comprises 3-methyl-1-phenyl-2-pirazoline-5-on or physiologically acceptable salts thereof as an active ingredient.

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.

The present disclosure is related to clear aqueous solutions of one or more bile acids and either an aqueous soluble starch conversion product or a non-starch polysaccharide. Solutions of the disclosure may be administered to a subject in conjunction with a pharmaceutical compound having a therapeutic effect in subjects with a neurodegenerative disease and / or a motor neuron disease. In some embodiments, the disease is amyotrophic lateral sclerosis.

A composition for treating, ameleliorating and / or preventing conditions associated with cognitive decline and / or motor neuron death comprise a fatty acid component enriched for one or more activated fatty acids and a nutraceutically acceptable excipient. A method for treating, ameliorating and / or preventing conditions associated with cognitive decline and / or motor neuron death includes administering a fatty acid component enriched for one or more activated fatty acids.