11 results about "Motor neurone" patented technology

It was discovered herein that neither the nuclear localization signal (NLS) nor the prion-like domain (PLD) of TDP-43 are required for in vitro embryonic stem cell culture and differentiation into motor neurons. ES cells expressing these TDP-43 mutants and differentiated into motor neurons that exhibit an ALS-like phenotype, from which the TDP-43 mutants redistribute to and accumulate in the cytoplasm, and the inability to regulate cryptic exon splicing, such that these cells can serve as a model for TDP-43 proteinopathies for testing candidate therapeutics that can dissipate such proteinopathies. In addition, these ES cells can be used to successfully generate non-human animals, e.g., mice, that also exhibit hallmark symptoms of ALS and can be used to test candidate agents useful for treating TDP-43 proteinopathies.

A device includes a first unit for skeletal muscle tissue formation; a second unit for motor neuron culture; a third unit for causing the first and second units to communicate with each other; and a pillar serving as a scaffold for skeletal muscle tissue formation. The first unit includes a first base material and a first culture tank formed in the first base material. The second unit includes a second base material and a second culture tank formed in the second base material. The third unit includes a third base material and an axon channel formed in the third base material, through which a bundle of axons passes. One end of the third unit is connectable to the second unit and cause the axon channel and the second culture tank to communicate with each other. A first opening part is formed to the other end of the third unit.

The application discloses a kind of construction methods and applications of motor neuron MNX1 reporter cell lines, belong to gene editing and stem cell technical field.The application develops a kind of expression motor neuron MNX1 reporter gene vector system by screening high-activity sgRNA, and vector system includes the guide vector of single-stranded guide RNA targeted to the vicinity of the termination codon of human motor neuron MNX1 gene, and the donor vector carrying the homologous arm in the vicinity of the termination codon of human motor neuron MNX1 gene.The application also includes the construction method of MNX1 reporter gene human pluripotent stem cell line into the above-mentioned vector system, the application can be applied to identify stem cell differentiation source human motor neuron, and the morphology and function of motor neuron are researched under the condition of living cell, provide important platform for the pathogenesis research of muscle-related disease, treatment method evaluation and new treatment target exploration.

The invention relates to a DNA origami-based intracellular delivery platform for precisely targeting motor neurons, a DNA origami structure (BioDoori) comprises M13mp18 single-stranded DNA, biotin chains (biotin-DNA), fluorescent chains (fluorophore-DNA) and unmodified staple chains, each side of the DNA origami structure is loaded with 1-30 fluorescent chains and 1-10 biotin chains, and the biotin chains are loaded with 1-30 fluorescent groups and 1-10 fluorescent groups. The nucleotide sequence of the staple chain is as shown in SEQ ID NO: 1-208. According to the nano origami structure disclosed by the invention, accurate and efficient specific targeting aiming at motor neuron cells is realized, and lysosome escape efficacy of a DNA origami carrier is improved in a breakthrough manner.

There is provided a method of promoting survival and / or function of an amyotrophic lateral sclerosis (ALS) or ALS-like motor, the method comprising contacting the motor neuron with an agent capable of reducing mitochondrial protein acetylation, particularly an agent selected from a deacetylase activator, such as nicotinamide (NAM) and 7-hydroxy-3-(4′-methoxyphenyl) coumarin (C12), or an acetyltransferase inhibitor, such as GCN5L1 siRNA of SEQ ID NO: 1. Also provided are related agents, oligonucleotides, uses and methods of identifying agents.

Described herein is the discovery that neither the nuclear localization signal (NLS) nor the prion-like domain (PLD) of TDP-43 is necessary for embryonic stem cell culture and differentiation into motor neurons in vitro. The ability of ES cells to express these TDP-43 mutants and differentiate into motor neurons that exhibit an ALS-like phenotype whereby the TDP-43 mutants redistribute to and aggregate in the cytoplasm and fail to regulate cryptic exon splicing allows these cells to act as a model of TDP-43 proteinopathy for the testing of candidate therapeutic agents that may resolve such proteinopathy. Additionally, these ES cells may be used to successfully generate non-human animals, e.g., mice, that also exhibit hallmark symptoms of ALS and that may be used in testing candidate agents useful in treating TDP-43 proteinopathies.

This invention discloses an Isl1-mimicking polypeptide, TAT-Isl1-ELE-1, containing 40 amino acids and consisting of a TAT sequence that promotes polypeptide entry into cells, a linker peptide, and a target sequence. The target sequence is amino acids 121-141 of the human Isl1 protein. The TAT-Isl1-ELE-1 polypeptide possesses Isl1-like functions and can effectively reprogram mouse spinal cord reactive astrocytes into motor neuron-like cells. Based on the amino acid sequence and spatial structure of this polypeptide, a novel small molecule drug can be designed, which can be synthesized in large quantities and is easy to operate clinically. This provides a new and viable approach for cell replacement therapy and regenerative medicine research after spinal cord injury (SCI), thereby achieving better SCI repair and functional reconstruction effects.

Disclosed herein are methods for treating a motor neuron disease such as amyotrophic lateral sclerosis (ALS) comprising administering mEphA4-Fc with an interval of greater than every week, for example administering mEphA4-Fc every two weeks, every three weeks, or every four weeks, and at a concentration of about 10 to about 40 mg / kg body weight of a subject.

The present disclosure relates to a method of treating or ameliorating symptoms of a motor neurone disease and improving motor neuron survival in a subject, more specifically treating or ameliorating symptoms of amyotrophic lateral sclerosis (ALS) and related neurodegenerative disorders. The treatment method comprises administering a Janus kinase (JAK) inhibitor in combination with one or more compounds selected from a glutamate antagonist and an N-methyl-D-aspartate (NMDA) receptor antagonist, in particular baricitinib in combination with riluzole and / or memantine, and compositions and kits thereof for same.

A system and method of use thereof for inducing colonic motility includes providing stimulations to a rectum of an individual. The stimulations include a plurality of low-frequency stimulations and a plurality high-frequency stimulations. The stimulations can be configured to activate sensory neurons and modulate the recto-colonic reflex pathway without directly activating motor neurons.