171 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.

Type 2 diabetes (T2D) is a clinical syndrome caused by insufficient insulin secretion for insulin requirements. Described herein are compositions and methods for microphysiological MPS models of disease (MODs) for diabetes. These platforms allow one to compare the effect of chronic β-cell stimulation in the presence and absence of patient specific immune cells in IPSC-derived islets from each group. Additionally, one can reproduce the T2D β-cell phenotype, using islets-on-chips will also be exposed to gluco-lipotoxicity. Likewise, skeletal muscle-on-chips are exposed to patient specific activated immune cells, variable motor neuron innervation and lipids characteristic of T2D.

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.

Methods, systems, and techniques for controlling actuators by using eye gaze technology such as in a wheelchair or bed, are provided. Example embodiments provide an Eye Gaze Actuator Control System (“EGACS”) which enables people with advanced motor neuron diseases or disabilities like amyotrophic lateral sclerosis or muscular dystrophy to use eye gaze technologies to control their actuators that control seating, bed positioning, and movement of motor-controlled devices. In one embodiment, the example EGACS comprises a display device, eye gaze sensor, eye gaze control application, and device interface(s) to one or more other devices that control aspects of a powered wheelchair, bed, vehicle, or other device. These components cooperate to control the powered wheelchair, bed, or vehicle using eye gaze technology as opposed to by manual control.

The present application relates to the use of a simulated weightlessness culture method and / or a mechanically sensitive ion channel inhibitor for in vitro culture of motor neurons; in addition, the invention also relates to a method for culturing motor neurons in vitro. The method comprises the step of culturing cells by using a simulated weightlessness culture method and / or a mechanical sensitive ion channel inhibitor as an auxiliary means.

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.

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.

Methods and systems for treating ALS and related motor neuron diseases using multi-site neuromodulation are disclosed.

Provided herein, inter alia, pharmaceutical formulations for oral administration of ROCK2 inhibitors (e.g., compound A). Also provided are methods for treating a neurodegenerative disease characterized by the degeneration of motor neurons, and particularly amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject in need thereof a therapeutically effective amount of a ROCK2 inhibitor.

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.

This application includes a mammalian mRNA expression construct for producing a protein or polypeptide, the mammalian mRNA expression construct including a modified Munc13-1 molecule.

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 subject matter described here relates to an enhancer specific to a subset of cholinergic neurons, that can control gene expression in a highly neuron-specific manner, wherein the enhancer is compatible with AAVs packaging and can induce gene expression or knockdown in cholinergic neurons in both post-natal and adult subjects.

A culture medium and a method using the said medium for obtaining motor neuron cells from human pluripotent stem cell-derived neuromesodermal stem cells (NMSCs) are provided. Furthermore, the present invention relates to obtaining motor neuron cells which can be used in research and clinical applications thanks to the said culture medium and method.

The present invention relates to a splice variant of a CERT1 protein that acts as a biomarker for a TDP-43 pathology, in particular motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but also other neurological diseases, such as Alzheimer's disease. In particular, the present invention relates to methods for identifying a splice variant of CERT1 comprising a cryptic peptide sequence, and to related methods of identifying a TDP-43 pathology and / or reduced TDP-43 function in a subject and to methods for predicting whether a therapy is likely to be successful. Also claimed are antibodies binding to the CERT1 splice variant and kits comprising the antibody.

The present invention addresses the problem of providing an antibody which excels at binding to the intravesicular domain of synaptotagmin 2.　Provided is a synaptotagmin 2 antibody capable of efficiently targeting a desired substance toward a motor neuron synapse.

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.

Methods and systems for treating ALS and related motor neuron diseases using multi-site neuromodulation are disclosed.

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.

To provide modeling of TDP-43 proteinopathy.SOLUTION: Disclosed herein is the discovery that neither nuclear localization signal (NLS) nor prion-like domain (PLD) of TDP-43 is necessary for embryotic stem cell culture and differentiation into motor neurons in vitro. The capability of ES cells to express TDP-43 variants and differentiate into neurons exhibiting an ALS-like phenotype (the TDP-43 variants 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. Further, these ES cells may be used for successfully generating a non-human animal such as a mouse exhibiting characteristic symptoms of ALS, for use in the search of candidate agents useful for the treatment of TDP-43 proteinopathy.SELECTED DRAWING: None

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.

As a result of performing an analysis exclusively on lower limb type and upper limb type ALS, excluding the bulbar palsy type ALS, among ALS for which it had been considered in existing reports that a reduction in Crtac1B was not observed, a significant correlation between the prognosis and the Crtac1B concentration in the cerebrospinal fluid was observed. Thus, it was discovered that Crtac1B is useful as a biomarker for predicting the prognosis of lower limb type and upper limb type ALS. As a result of analyzing the association between the motor function and the Crtac1B concentration in the cerebrospinal fluid before and after treatment in SMA patients treated with an SMA therapeutic agent, it was found that the Crtac1B concentration in the cerebrospinal fluid reflects the disease progression of SMA, and that Crtac1B is useful as a biomarker for diagnosing the therapeutic effect by the SMA therapeutic agent.

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 invention addresses the problem of providing an antibody that excels at binding to the intravesicular domain of synaptotagmin 2.　Provided is a synaptotagmin 2 antibody capable of efficiently targeting a desired substance toward motor neuron synapses.

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).

The present invention addresses the problem of providing an excellent antibody that binds to an intravesicular domain of a synaptic vesicle glycoprotein 2C.　Provided is a synaptic vesicle glycoprotein 2C antibody capable of efficiently targeting a desired substance toward a motor neuron synapse.

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.

In various aspects and embodiments provided are compositions and methods for treating a patient that has ALS (or Lou Gehrig's disease or motor neuron disease). More specifically, the disclosure in some embodiments includes administration of a β-AR agonist (such as a β-agent) and optionally a peripherally acting β-blocker (PABRA) to a patient in need thereof.