84 results about "Motor neurone" 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 belongs to the technical field of gene engineering, and provides shRNA (short hairpin Ribonucleic Acid) for knocking down BST2 gene expression, a recombinant vector and application of the shRNA, and the shRNA comprises Bst2-shRNA-1 or Bst2-shRNA-2; the Bst2-shRNA-1 comprises a positive-sense strand of which the nucleotide sequence is as shown in SEQ ID NO. 1 and an antisense strand of which the nucleotide sequence is as shown in SEQ ID NO. 2; the Bst2-shRNA-2 comprises a positive-sense strand of which the nucleotide sequence is as shown in SEQ ID NO. 3 and an antisense strand of which the nucleotide sequence is as shown in SEQ ID NO. 4. The shRNA disclosed by the invention plays an important role in inhibiting non-infectious aseptic inflammation, can effectively delay the ALS attack time and protect motor neurons, has a very good application prospect, and also provides a direction and a technical basis for searching, researching and developing new therapeutic drugs for treating ALS.

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.

The present disclosure provides recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and / or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and / or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, “treatment” generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and / or by a decrease in the duration of such symptoms.

The present disclosure provides recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and / or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and / or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, "treatment" generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and / or by a decrease in the duration of such symptoms.

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.

The present invention belongs to the field of traditional Chinese medicine, and particularly relates to the use of a traditional Chinese medicine composition in the preparation of a medicament for preventing and / or treating amyotrophic lateral sclerosis. Specifically, the traditional Chinese medicine composition is prepared from Schizonepeta tenuifolia Briq., Saposhnikovia divaricata (Turcz.) Schischk., Notopterygium incisum Ting ex H. T. Chang, Heracleum hemsleyanum Diels, Bupleurum chinense DC., Peucedanum praeruptorum Dunn, Ligusticum chuanxiong Hort., Citrus aurantium L. var. amara Engl., Poria cocos (Schw.) Wolf, Platycodon grandiflorus (Jacq.) A. DC., and Glycyrrhiza uralensis Fisch. The results of pharmacodynamic experiments show that the traditional Chinese medicine composition provided by the present invention can improve the limb strength of amyotrophic lateral sclerosis model mice, prolong the survival period, maintain weight gain, has the effects of delaying the muscle atrophy process and delaying motor neuron apoptosis, and has a definite curative effect on treating amyotrophic lateral sclerosis.

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.

The present disclosure provides recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and / or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and / or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, “treatment” generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and / or by a decrease in the duration of such symptoms.

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.

Disclosed is a method of determining whether a human subject is not a carrier of spinal muscular atrophy (SMA). This method includes the steps of (i) collecting a genomic deoxyribonucleic acid (DNA) sample from a human subject; (ii) screening the genomic DNA sample to determine the human subject's copy number of survival of motor neuron 1 (SMN1) gene and whether one of the copies of the SMN1 gene is positive for a polymorphism associated with non-carriers of SMA having two copies of the SMN1 gene; and (iii) determining the human subject as not a carrier of SMA if the human subject includes two copies of the SMN1 gene with one of those copies being positive for the polymorphism. Also disclosed is a method of determining whether an individual has a decreased risk of being a carrier of spinal muscular atrophy (SMA), where the individual is identified to have a decreased risk of being a carrier of SMA when the individual has two copies of the SMN1 gene with one of those copies being positive for the polymorphism.

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 recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and / or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and / or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, "treatment" generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and / or by a decrease in the duration of such symptoms.

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 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.

Disclosed herein include systems, devices, computer readable media, and methods for paralog genotyping, such as determining a copy number of survival of motor neuron 1 gene and genotyping cytochrome P450 family 2 subfamily D member 6 gene using a Gaussian mixture model comprising a plurality of Gaussians each representing a different integer copy number.

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 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.

The invention discloses an adeno-associated virus plasmid as well as a construction method and application thereof. The construction method of the adeno-associated virus plasmid comprises the following steps: obtaining an adeno-associated virus plasmid skeleton and a lentivirus plasmid skeleton containing s i PTEN and coSMN; respectively cutting off s i PTEN and coSMN in the lentivirus plasmid skeleton by using a first incision enzyme and a second incision enzyme; a first incision enzyme and a second incision enzyme are respectively used for cutting off ss SOD1 in an adeno-associated virus plasmid skeleton and inserting s PTEN, and cutting off GFP and inserting coSMN, so that the adeno-associated virus plasmid containing s PTEN and coSMN at the same time is obtained. According to the adeno-associated virus plasmid, the coSMN and the s i PTEN have a synergistic effect, so that a PI 3 kinase pathway is activated, and death of motor neurons in a spinal muscular atrophy attack process is reduced.

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 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.

Methods and compositions relating to motor neurons derived from induced pluripotent stem cells of subjects having a neurodegenerative disease, where the motor neurons exhibit phenotypes characteristic of the neurodegenerative disease, are provided herein. In particular, the present invention provides methods for screening putative therapeutic agents and methods for diagnosing living subjects as having a neurodegenerative disease. In addition, the present invention provides therapeutic gene transfer methods for treating or preventing a neurodegenerative disease in a subject in need thereof.

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.