94 results about "Primary motor neuron" patented technology

The invention belongs to the technical field of medical instruments, and particularly relates to a spinal epidural ventral side double-wing-shaped stimulation electrode and motion function reconstruction system, the spinal epidural ventral side double-wing-shaped stimulation electrode and motion function reconstruction system comprises two wing panels, each wing panel comprises a flexible substrate, the flexible substrate is provided with two bifurcated preset-curvature double-wing structures; the electrode contact array is integrated on the flexible polar plate through a bonding pad; according to the double-wing-shaped flexible substrate, through a double-wing structure with a preset curvature, after being unfolded under the driving of a nickel-titanium alloy framework, the double-wing-shaped flexible substrate accurately covers a spinal cord ventral side and double-side anterior angle motor neuron pool, and the problem that a traditional single-piece / rod-shaped electrode can only cover a back side sensing area and cannot cover a back side sensing area is solved. The ventral motor neuron group cannot be directly activated; a stimulation target spot is transferred to a ventral functional core area from a dorsal non-target area for the first time, and the anatomical suitability bottleneck of motor function reconstruction is solved.

The invention provides a motor neuron and myotubular cell co-culture method and model and application thereof. The motor neuron and myotubular cell co-culture method comprises the steps that motor neuron is cultured to form a neural network, and a motor neuron culture layer with the formed neural network is obtained; culturing myoblasts, inducing differentiation to form fine myotube cells, adding a mitosis inhibitor, and digesting and separating to obtain the fine myotube cells; and inoculating fine myotubular cells to the motor neuron culture layer with the formed neural network, and co-culturing. The co-culture method disclosed by the invention overcomes the limitation of a traditional nerve cell and muscle cell co-culture method, and has the advantages of simplicity, convenience, high efficiency, stability and the like. The method not only provides an effective experimental tool for related basic research of neuromuscular joint formation, physiological functions and the like, but also has wide application prospects in the fields of neuromuscular disease research, drug screening, toxicological research, gene therapy and the like.

The present invention relates to a system and method configured for analysing acoustic parameters of speech to detect, diagnose, predict and / or monitor progression of a condition, disorder, or disease, and more particularly, any of paediatric and adult neurological and central nervous system conditions including but not limited to low back pain, multiple sclerosis, stroke, seizures, Alzheimer's disease, Parkinson's disease, dementia, motor neuron disease, muscular atrophy, acquired brain injury, cancers involving neurological deficits, paediatric developmental conditions and rare genetic disorders such as spinal muscular atrophy. The system and method extracts a first formant data set from words spoken by an individual and uses these to classify the vowels in the words on a first computing device, such as a mobile smart phone equipped with a microphone into which an individual speaks. The system stores at least some of these frequencies for the vowel formants in a second formant data set as a recorded file and provides the second formant data set as input to acoustic metrics to generate score data from which an assessment is made to determine the articulation level of the vowels in the words spoken by the individual, allowing allow for detection, diagnosis, prediction and / or monitoring progression of the condition, disorder, or disease.

Provided is a medicament for treating a disease related to motor neuron injury. The medicament comprises: a circular RNA having a circBank ID of hsa_circPTPRN2_018, and a proper diagnosis module and a drug carrier. Also provided is use of a circular RNA in preparing a medicament for diagnosing and treating a disease related to motor neuron injury.

In a method for inducing differentiation into neuromuscular junctions according to the present disclosure, the neuromuscular junctions are induced by: preculturing human pluripotent stem cells in a medium containing activin, bFGF, a WNT signal inhibitor, a BMP signal inhibitor, and a ROCK signal inhibitor; then culturing the stem cells in a medium containing bFGF, a ROCK signal inhibitor, a WNT signal activator, and a TGFβ signal inhibitor to differentiate into neuromesodermal cells; culturing the neuromesodermal cells in a medium containing a BMP signal inhibitor, a TGFβ signal inhibitor, a retinoic acid activator, and an SHH signal activator to differentiate into skeletal muscle progenitor cells and spinal motor neuron progenitor cells in the same culture dish; and culturing these progenitor cells in a medium for cell maturation containing BDNF, GDNF, AA, and dbcAMP.

The invention discloses an analysis method for storage of single vesicles in ventral spinal cord motor neuron-like organs induced and differentiated by an iPSC technology. The method sequentially comprises the steps of construction of an acetylcholine nano microelectrode sensor interface, recovery and culture of human pluripotent stem cells, directional differentiation of spinal cord movement organs and storage and detection of single vesicle acetylcholine. A new thought and a new method are provided for monitoring the level of acetylcholine stored in the single vesicles at the single cell level, and the method has important theoretical significance and wide practical value in research of pathogenesis of diseases, drug screening and the like in the field of neuroscience.

The present invention relates to sulphate salts of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine and pharmaceutically acceptable solvates thereof, for use in the treatment and / or prevention of motor neuron diseases and neuromuscular junction disorders.

Disclosed herein are embodiments of a compound that inhibits c-Abl tyrosine kinase (also referred to herein as “c-Abl”). The compound embodiments described herein are novel c-Abl inhibitors that can bind to c-Abl at an allosteric site and inhibit its activity in various pathways. The compound embodiments also are capable of crossing the blood brain barrier and therefore are useful in inhibiting c-Abl activity as it affects pathways and / or proteins in the brain. The compound embodiments described herein are effective therapeutic agents for treating diseases involving c-Abl, such as cancers, motor neuron diseases, and neurodegenerative diseases. Also disclosed herein are embodiments of methods for making and using the c-Abl inhibitory compound embodiments.

The present invention relates to splice variants of the CERT1 protein that act as biomarkers for TDP-43 pathology, particularly motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), as well as other neurological diseases such as Alzheimer's disease. In particular, the present invention relates to a method for identifying splice variants of CERT1 comprising cryptic peptide sequences, as well as related methods for identifying TDP-43 pathology and / or TDP-43 dysfunction in a subject, and a method for predicting the likelihood of successful treatment. Antibodies that bind to CERT1 splice variants and kits comprising said antibodies are also claimed.

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.

This application provides a novel differentiation factor for direct cross-differentiation from somatic cells to motor neurons, a composition containing the differentiation factor, a method for direct cross-differentiation using the composition, and uses for the novel differentiation factor. [Solution] A composition for direct cross-differentiation from somatic cells to induced motor neurons, the composition comprising (A) the Gsta4 protein or nucleic acid coding therefor; and (B) one or more proteins selected from Ascl1, Brn2, Myt1L, Hb9, ISL1, Lhx3, Ngn2 and NeuroD1 or nucleic acid coding therefor; and further comprising a viral capsid for transmitting (A) or (B).

1. Name of the product in this design: Walking Assistive Rehabilitation Device. 2. Purpose of this design: It is used in a walking rehabilitation device, which is a wearable functional neurostimulation instrument used for lower limb rehabilitation and recovery of muscles damaged by motor neurons. 3. The key design feature of this product is its shape. 4. The image or photograph that best illustrates the design's key points: 3D view 1. 5. Other circumstances requiring explanation: The human lower limb model is a supporting element and is not part of the content for which protection is sought.

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.

Disclosed are 20-hydroxyecdysone and the derivatives thereof, intended for use in the treatment of a neuromuscular disease such as spinal muscular atrophy or amyotrophic lateral sclerosis, or more particularly in the treatment of a specific disorder of the motor neurons causing alterations in the muscular function occurring in the context of these neuromuscular diseases.

The invention relates to the technical field of medical instruments, in particular to an anatomical adaptive spinal cord and waist expansion epidural abdominal side electrode which comprises an electrode body, a plurality of contacts are arranged on the electrode body, an electrical stimulation generating device is connected to the outside of the electrode body, and the electrode body is configured to be implanted into the epidural abdominal side of a human spinal cord and waist expansion area. The electrode is directly implanted into the outer ventral side of the spinal epidural to stimulate the spinal motor neurons in a targeted manner, so that the problem of energy shunt of dorsal indirect stimulation is avoided, target neurons are effectively activated under low stimulation intensity, and side effects such as stabbing pain and numbness of a patient are reduced.

Presented herein are methods of identifying a subject who has, or is at risk of developing a motor neuron disease, specifically Amyotrophic Lateral Sclerosis (ALS), and / or Primary Lateral Sclerosis (PLS), that includes determining a presence or amount of two or more micro-RNAs (miRNAs) selected from miR-199a-3p, miR-4454, miR-10b-5p, miR-151a-5p, miR-199a-5p, miR-151a-3p, miR-146a-5p, and / or miR-29b-3p in a subject's circulating blood, without determining a presence or amount of the miRNAs from neural-derived exosomes. Also presented herein are methods of preventing, treating, or delaying the onset of a motor neuron disease, specifically ALS and / or PLS.

The present disclosure provides methods of treatment of neurodegenerative disease, such as a motor neuron disease, in subjects in need thereof. A therapeutically effective dose of a suitable mast cell stabilizer may be administered to suitable subjects, wherein the suitability of a subject is determined by the rate of progression of the disease over time or by the severity of the disease. A therapeutically effective dose of a suitable mast cell stabilizer may be administered to suitable subjects, wherein the suitability of a subject is determined by subject genotype and / or family genotypes or medical history. In certain embodiments, the therapy may comprise a cromolyn homolog salt, and suitable subjects are persons with amyotrophic lateral sclerosis (ALS). In certain embodiments, the subjects are patients with slow progressing ALS and / or the subjects have mild to moderate ALS. In certain embodiments, the subjects are persons with sporadic ALS or persons without familial ALS.

This invention describes artificial expression constructs for regulating gene expression in target types of central nervous system cells. By using the artificial expression constructs of this disclosure, it is possible to express or modify the expression of synthetic genes in spinal motor neurons, including SpP1 spinal motor neurons, Parg spinal motor neurons, Ogdh1 spinal motor neurons, and ChAT spinal motor neurons; α motor neurons, including Chodl spinal motor neurons; γ motor neurons; spinal excitatory motor neurons, including Mafa excitatory neurons, Esrrg Trhr excitatory neurons, and Slc17a6 spinal excitatory neurons; spinal inhibitory neurons, including Slc6a5 spinal inhibitory neurons; whole spinal neurons, including Esrrg spinal motor neurons and types of neurons found throughout the spinal cord; cerebrospinal fluid contact neurons, including Poln spinal motor neurons; and non-neuronal cells of the spinal cord, including astrocytes and oligodendrocytes.

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.

Disclosed herein are methods and related compositions for determining a likelihood that a subject has a motor neuron disease (e.g., amyotrophic lateral sclerosis) based on levels of a combination of lipid biomarkers in a biological sample from the subject. Also disclosed are methods for determining a rate of progression of a motor neuron disease based on changes in lipid biomarker levels in a subject over time. Also disclosed are methods for detecting the presence and / or determining the level of at least three lipid biomarkers disclosed herein in a subject suspected of suffering from a motor neuron disease. Also disclosed are related kits useful for carrying out the disclosed diagnostic or prognostic methods.

The invention belongs to the technical field of nerve regulation and control, and relates to a 64-way nerve regulation and control system and method for directly targeting spinal cord motor neurons. The method comprises the steps that the low-power-consumption microprocessor configures a result through an operational analysis mode and then sends out a positive pulse trigger control signal and a negative pulse trigger control signal, and the 64-path positive / negative pulse trigger module selectively sends out positive / negative pulse stimulation signals according to the control signals; the 64-path positive / negative current and voltage feedback module samples the intensity of stimulation signals sent by the 64-path positive / negative pulse trigger module and sends the sampled signals back to the low-power-consumption microprocessor through an ADC0; and the low-power-consumption microprocessor starts current and voltage detection to analyze whether the current intensity meets the requirement or not. According to the method, 64 paths of electrodes can be randomly paired and cooperatively controlled, and frequency, current, voltage and pulse width parameters are controlled to be randomly adjustable in a set range, so that cooperative control on muscles and joints of lower limbs is realized, and paralyzed patients of different degrees can realize coordinated autonomous movement.

This invention belongs to the field of molecular biology and discloses a recombinant adeno-associated virus (AAV) vector and its applications. The recombinant AAV vector of this invention comprises an AAV capsid and sequence elements, including an EFS promoter sequence and a sequence encoding a motor neuron survival protein. The recombinant AAV vector provided by this invention can avoid the toxicity caused by overexpression of SMN1, stably maintain the SMN1 protein level in vivo within the therapeutic window, prolong the survival time of SMA mice, increase mouse body weight, improve the development of motor neurons and skeletal muscle-related tissues, and restore neuronal physiological function. This invention employs a gene therapy strategy and can be used to prevent, alleviate, or treat neurological diseases.

The invention relates to a composition for inducing reprogramming of mesenchymal stem cells and application of the composition, and belongs to the technical field of biological medicine. According to the present invention, it is firstly found that the composition of CHIR99021, Y27632, SB431542 and purmorphamine can induce the reprogramming of mesenchymal stem cells into cholinergic motor neurons and glutamic acid energy interneurons, the cholinergic motor neurons are mainly adopted, and the induction efficiency of the composition is the highest; and inoculating the mesenchymal stem cells onto the silk fibroin scaffold, adding CYSP for induced culture, and finding that the induced neuron-like cells wrap the periphery of silk fibroin fibers to form a transplantable neuron network. When the neural network is transplanted into a spinal cord injury rat model, the deposition of collagen in a spinal cord injury cavity of a rat transplanted with the neural network is reduced, host neurons are saved, nerve fiber regeneration is promoted, and the injured spinal cord is repaired.

The subject matter described here relates to methods, compositions, and vectors for treating Amyotrophic Lateral Sclerosis (ALS) in a subject in need thereof. In certain aspects, the method comprises administering to the subject a composition comprising adeno-associated viruses (AAVs), wherein the AAVs comprise a nucleic acid sequence comprising an enhancer sequence and encoding one or more transcription factors that control gene expression in nascent motor neurons, wherein the enhancer is capable of driving a motor-neuron specific expression of the one or more transcription factors and wherein the one or more transcription factors are expressed in motor neurons of the subject.

Provided herein are methods for decreasing Ataxin-2 mRNA expression. Such methods are useful to ameliorate symptoms of Ataxin-2 associated diseases. Such Ataxin-2 associated diseases include amyotrophic lateral sclerosis (ALS). Such symptoms include loss of motor function, reduced CMAP amplitude, denervation, and loss of motor neurons.

Disclosed herein are compound embodiments that are useful for treating a variety of diseases, particularly neurological diseases, motor neuron diseases, copper deficiency-related diseases, and / or mitochondrial deficiencies. The compound embodiments described herein also can be used in PET methods. Also disclosed herein are embodiments of methods of making and using the compound embodiments, as well as pharmaceutical formulations comprising the disclosed compound embodiments.

The invention provides arbutin-28beta-pyroglutamyl ester. The arbutin-28beta-pyroglutamyl ester is prepared by adopting a two-stage liquid fermentation process to culture a Circinella muscae CGMCC (China General Microbiological Culture Collection Center) 3.2695 strain. The arbutin-28beta-pyroglutamyl ester is a natural triterpenoid metabolite synthesized through microbial conversion for the first time, has good activity of promoting the growth of motor neurons, and can be used for preparing drugs for treating nervous system diseases.

The present application belongs to the technical field of nerve regulation, and relates to a 64-channel nerve regulation system and method for directly targeting spinal motor neurons. The method comprises the following steps: a low-power microprocessor analyzes and configures mode results through operation, and then sends out positive pulse trigger control signals and negative pulse trigger control signals; a 64-channel positive / negative pulse trigger module selectively sends out positive / negative pulse stimulation signals according to the control signals; a 64-channel positive / negative current voltage feedback module samples the stimulation signal intensity sent out by the 64-channel positive / negative pulse trigger module, and sends the sampling signals back to the low-power microprocessor through ADC0; and the low-power microprocessor enables current voltage detection, and analyzes whether the current intensity meets the requirements. The method can realize the arbitrary pairing and cooperative control of 64 electrodes, and the control frequency, current, voltage and pulse width parameters are all adjustable within the set range, so as to realize the cooperative control of lower limb muscles and joints, and make different degrees of paralyzed patients realize coordinated autonomous movement.

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.

An electromyography (EMG) strap and a wearable electronic device are provided. The EMG strap includes a flexible strap body; a flexible printed circuit board (FPCB), housed within the flexible strap body; a surface electromyography (sEMG) sensor assembly, disposed on the FPCB, where the sEMG sensor assembly is exposed from the flexible strap body and is configured to collect an EMG signal and pre-process the EMG signal to obtain a pre-processed analog signal; and a board-to-board (BTB) connector, disposed on the FPCB and electrically connected to the sEMG sensor assembly. The EMG strap can not only help in diagnosing conditions like muscular dystrophy and motor neuron disease but also play a pivotal role in developing advanced prosthetic devices that respond to muscle signals.