83 results about "Neurofibra" patented technology

The disclosure features methods for treating at least one symptom of neurofibromatosis type 1, treating at least one symptom of dystrophic scoliosis, or inducing bone healing by administering a soluble alkaline phosphatase (sALP) to the patient.

A method for treating neurodegenerative diseases or disorders, comprising administering to a subject in need thereof a GLP-1 receptor agonist or a composition thereof. A medicament or a composition or a treatment method using a GLP-1 receptor agonist can significantly improve behavioral abilities such as learning and memory, daily self-care, exercise and emotion related to neurodegenerative diseases or symptoms in a subject and improve pathological states such as brain Aβ plaque deposition, neurofibrillary tangles and neuronal cell inflammation in the subject.

The present disclosure relates to a method for treating certain tumors or cancers, e.g., plexiform neurofibroma (PN), plexiform neurofibroma associated with neurofibromatosis type 1 (NF1-PN), by administering mirdametinib or a pharma- ceutical acceptable salt thereof to a patient in need thereof, e.g., by certain administration schemes.

The invention relates to the technical field of neurosurgery navigation, in particular to a neurosurgery brain puncture path accurate planning method and system.The neurosurgery brain puncture path accurate planning method comprises the following steps that by obtaining a preoperative brain function area image and nerve fiber bundle data, a function area range and sensitivity are extracted, a focus and cranial entry point path set is constructed, and a path set is established; the method comprises the steps of analyzing the distance between a path and a functional area and a fiber bundle included angle, calculating a functional interaction risk, dividing path sections and calculating the distances to a blood vessel, a ventricle and the functional area, generating obstacle field intensity and calculating a gradient difference, constructing a risk map, scoring candidate paths, and screening an optimal path to generate a puncture result. The method comprises the following steps: extracting a brain function region range and a fiber bundle direction, introducing a function sensitivity parameter, improving tiny damage identification, calculating obstacle field intensity in a path segmentation manner, forming a gradient, dynamically identifying a high-risk region, grading and screening candidate paths by integrating risk factors, performing function protection and risk reduction, and improving path planning refinement and safety.

The present application relates to the technical field of medical information processing and intelligent disease prediction, in particular to a neurofibromatosis prediction method based on clinical medical information. The method comprises the following steps: acquiring multi-modal clinical medical information with time labels; performing anatomical system classification processing, extracting clinical feature nodes and calculating correlation, and establishing an initial multi-system prediction network graph; determining the asynchronous graph node feature aggregation rate according to the feature update rate difference of adjacent nodes under different time labels, performing local feature diffusion processing, and determining a global multi-system prediction network graph; further determining the cross-domain evolution incubation period weight, the phenotype cascade transfer probability matrix and the disease topology state information entropy, and determining the neurofibromatosis prediction result accordingly. The present application solves the contradiction of long-term and ineffective consumption of a large amount of computing resources to cope with low-frequency but high-impact clinical events, and optimizes the trade-off relationship between risk identification accuracy and system response timeliness.

Aspects of the disclosure relate to compositions and methods of treating certain genetic disease (e.g., Neurofibromatosis type I) by delivering functional neurofibromin 1(NF1) protein (e.g., mini-NF1 protein and / or full-length NF1 protein) to target cell (e.g., cells and / or tissue of a subject). The disclosure is based, in part, on isolated nucleic acids (e.g., rAAV vectors) and rAAVs engineered to express a functional NF1 protein (e.g., mini-NF1 protein and / or full-length NF1 protein) or variants thereof.

The present invention relates to the technical field of biomedicine. Provided are a lentiviral vector for the gene therapy of neurofibromatosis type 2 (NF2), and the use thereof. The technical problem to be solved is how to provide a lentiviral vector suitable for treating neurofibromatosis type 2. Specifically, disclosed is a lentiviral vector for the gene therapy of neurofibromatosis type 2. The vector framework of the lentiviral vector is pPD5, and the sequence of the pPD5 is subjected to at least one of the following substitutions: A1) a substitution of the NF2 encoding sequence of the pPD5 with sequence 1; A2) a substitution of the promoter of the pPD5 with sequence 2; and A3) a substitution of the control element of the pPD5 with sequence 3. The improved vector can effectively inhibit tumor growth and can be used for the treatment of neurofibromatosis type 2, and thus lays the foundation for research on the lentiviral vector for the treatment of neurofibromatosis type 2.

Provided are gene therapy vectors, such as adeno-associated virus (AAV), designed for treatment of mutations in the neurofibromin 1 (NF1) gene. The disclosed gene therapy vectors provide a mini-NF1 cDNA to a subject in need which results in expression of a functional NF1 protein. Also provided are compositions, nanoparticles, extracellular vesicles, exosomes, or vector comprising the NF1 gene with nerve-cell specific and Schwann-cell specific promoters and methods of using the mini-NF1 gene with nerve-cell specific and Schwann-cell specific promoters in treating neurofibromatosis type 1. Also provided are novel mini-NF1 gene constructs.

The application belongs to the field of medicine, and particularly relates to application of axitinib in preparation of a medicine for treating plexiform neurofibroma. In the medicine, axitinib serves as the only effective component or one of the effective components. When axitinib serves as one of the effective components in the medicine, the effective components further include a MEK inhibitor. The MEK inhibitor is selected from one of selumetinib and trametinib. The application proves that axitinib can play a role in inhibiting plexiform neurofibroma (pNF) by targeting OTUD3, an important gene for promoting pNF progression. Moreover, axitinib is a drug that has been used for clinical treatment, and has good safety. The research result of the application shows that the combination use of axitinib and the MEK inhibitor can improve the inhibitory effect on neurofibroma.

The present disclosure relates to an oral dosage form, such as a capsule, comprising (a) mirdametinib having a d90 no more than 250 microns, a d50 no more than 50 microns, or both, and (b) one or more pharmaceutically acceptable excipients. These dosage forms are useful in the treatment of tumors and cancers, such as plexiform neurofibromas (PN), plexiform neurofibromas associated with neurofibromatosis type 1 (NF1-PN), high grade glioma (HGG), low grade ovarian cancer, Langerhans cell histiocytosis (LCH), brain cancer, and a cancer that has metastasized to a patient's brain. The disclosure also related to improved dosage regimens for mirdametinib treatments.

The invention relates to a multiplex fluorescent quantitative PCR (polymerase chain reaction) primer, a probe and a kit for detecting neurofibroma I type NF1 gene variation sites, and provides four NF1 gene mutation sites found for the first time, the four variation sites are NF1 gene c.21002105delinsAG, c.4561dup, c.6421del and c.6797dup variation sites respectively, and the mutation sites of the NF1 gene c.21002105delinsAG, the c.4561dup, the c.6421del and the c.6797dup can be used for detecting neurofibroma I type NF1 gene mutation sites. Meanwhile, the invention also provides a specific primer, a probe composition and a kit for detecting the NF1 gene variation site of the neurofibromatosis I type for screening or diagnosing the neurofibromatosis I type. The NF1 gene pathogenic variation spectrum is expanded, and a basis is provided for diagnosis and genetic counseling of the neurofibroma type I. The kit disclosed by the invention can comprehensively cover four new pathogenic variation sites of the NF1 gene related to the neurofibroma type I, is high in accuracy, and can specifically detect the pathogenic variation sites.

A biomarker composition for predicting susceptibility to a therapeutic agent for neurofibromatosis by using Ras activity; and a pharmaceutical composition for preventing or treating neurofibromatosis, including a Ras activity inhibitor. The biomarker composition can accurately diagnose susceptibility to a therapeutic agent for neurofibromatosis by measuring the expression levels of a GTP-bound and activated Ras (Ras-GTP) protein and an activated p-ERK protein or a gene encoding the same in a biological sample of an individual. The pharmaceutical composition inhibits the activity of Ras proteins, and thus can be effectively used for the prevention or treatment of neurofibromatosis in which the activity of the Ras proteins is increased.

Among the various aspects of the present disclosure is the provision of methods for inhibiting neuronal activity in NF1 tumors. One aspect of the disclosure provides for a method of inhibiting tumor growth comprising administering a neuronal activity inhibiting agent to a subject in need thereof. Another aspect of the disclosure provides for a method of attenuating neuronal excitability, activity-regulated mitogen production, and tumor progression comprising administering a neuronal activity inhibiting agent to a subject in need thereof. Yet another aspect of the disclosure provides for a method of activating HCN channels in a subject comprising administering a neuronal activity inhibiting agent to a subject in need thereof. Yet another aspect of the disclosure provides for a method of treating brain or and nerve tumors in Neurofibromatosis type 1 (NF1) comprising administering a neuronal activity inhibiting agent to a subject in need thereof.

The invention provides a culture method of a neurofibroma organ. The balling culture medium of the neurofibroma organ comprises EGF (epidermal growth factor) and FGF (fibroblast growth factor) with the concentration of 200-250ng The organoid culture method comprises the following steps: digesting neurofibroma tissue blocks to prepare a single-cell suspension; the single-cell suspension is placed in a culture dish treated by polylysine, a Schwann cell culture medium is added to be cultured for 24 hours, the Schwann cell culture medium contains forsklin and beta-heragulin needed by Schwann cell enrichment, and Schwann cell enrichment liquid is obtained; collecting Schwann cell enrichment liquid, adding the balling culture medium and Y-27632, culturing for 6-12 hours, collecting cells, adding the balling culture medium, and culturing for 7-14 days. The tumor ball culture method comprises the following steps: culturing the organoid according to the method, digesting the organoid and culturing. According to the present invention, the Schwann cell screening step is added, the components of the balling culture medium are improved, and the Y-27632 is added, such that the problems of small tumor ball number and small size are solved, and the stable neurofibroma organ can be formed.

The application discloses application of FTY720 as a PP2A phosphatase activator in preparation of a medicine for treating type I neurofibromatosis. The application first uses FTY720 for treatment of type I neurofibromatosis, and proves that FTY720 significantly inhibits formation of neurofibromas by non-specifically activating PP2A phosphatase. In-vivo experimental results show that FTY720 as a single drug can significantly inhibit tumor growth, and a synergistic effect is presented when FTY720 is combined with a MEK inhibitor, and tumor growth is almost completely inhibited. In-vitro cell experiments show that FTY720 as a single drug or in combination with MEKi treatment can inhibit tumor Schwann cells from forming tumor spheres, inhibit cell proliferation and migration, and induce tumor cell apoptosis. The application overcomes the drug resistance problem existing in the prior art MEK inhibitor, and provides a new treatment strategy for type I neurofibromatosis. FTY720 is an FDA-approved drug, and has good safety and drugability, and has high clinical conversion potential.

The invention relates to a multiplex fluorescent quantitative PCR (polymerase chain reaction) primer, a probe and a kit for detecting neurofibroma I type NF1 gene variation sites, and provides four NF1 gene mutation sites found for the first time, the four variation sites are NF1 gene c.21002105delinsAG, c.4561dup, c.6421del and c.6797dup variation sites respectively, and the mutation sites of the NF1 gene c.21002105delinsAG, the c.4561dup, the c.6421del and the c.6797dup can be used for detecting neurofibroma I type NF1 gene mutation sites. Meanwhile, the invention also provides a specific primer, a probe composition and a kit for detecting the NF1 gene variation site of the neurofibromatosis I type for screening or diagnosing the neurofibromatosis I type. The NF1 gene pathogenic variation spectrum is expanded, and a basis is provided for diagnosis and genetic counseling of the neurofibroma type I. The kit disclosed by the invention can comprehensively cover four new pathogenic variation sites of the NF1 gene related to the neurofibroma type I, is high in accuracy, and can specifically detect the pathogenic variation sites.

The present disclosure is directed to a bio-feedback sensor in combination with AI and ML that can be implemented to optimize neuromodulation parameters for the management of a medical condition such a type II diabetes. The bio-feedback obtained by the sensors is optimized by the ML tools to predict and recommend the upregulation or downregulating the neuroregulators to modulate treatment. The algorithms could also learn to sense a life-threating pathological state, or bio-chemical imbalance, and in the case of diabetes a life-threating low blood sugar level the system overrides to stimulate the target fibers that control organs to regulate blood glucose levels.

Disclosed are devices, systems and methods for non-invasive neuromodulation system for treating inherited or acquired retinal, choroidal and optic nerve disorders caused by acute or chronic dysregulated reduced ocular blood flow (OBF) and / or energy failure by up regulation of trigemino-vascular system (TVS), trigeminal autonomic brain reflexes (TABRs) and pancreatic trigemino-vagal reflex (TVR) through stimulation of ophthalmic nerve (V1), more specifically but not limited to SP, and CGRP containing unmyelinated C nerve fibers. The invention, in some embodiments thereof, relates to the methods for enhancing SP and CGRP expression in neurovascular tissue of the retina and choroid. The invention, in some embodiments thereof, relates to SP / CGRP mediated pathways, including those involved in vasodilatation, augmentation of OBF, RPE proliferation, prevention of apoptosis, suppressing neuroinflammation, promoting migration and differentiation of vascular endothelial cells as well as mobilization of endogenous mesenchymal stem cells (EMSCs) from the bone marrow to the circulation to accelerate tissue repair. The site of stimulation of V1 nerve includes but not limited to; nasal vestibule nasal bridge, forehead, and upper eyelids. Additionally or alternatively, the subject's sympathetic nervous system (SNS) is down regulated by sympatholytic agents specifically antioxidants. The subject's TVS and autonomic nervous system (ANS) are modulated in a manner that is effective to treat the subject for retinal, choroidal and / or optic nerve disorders. In some embodiments, the devices are handheld, portable with nose supported, having one or more intra-nasal or extra-nasal application heads. The signal can include vibration, chemical, ultrasonic, optical, electrical, hybrid electro-optical or combination of two or more of these types of stimuli. The invention, in some embodiments thereof, relates to a method for decreasing vascular resistance, enhancing vasodilatation in ophthalmic artery and its branches by the release of Vasoactive intestinal peptide (VIP), substance P and CGRP thereof increasing OBF to the retina, choroid and optic nerve in subject's with acute or chronic dysregulated, reduced OBF. The invention, in some embodiments thereof, is also relates to the methods for improving delivery of oxygen, glucose, vitamin A, humoral mediators, growth factors, stem cells and pharmacological agents to the targeted tissues of the retina, choroid and optic nerve. The invention, in some embodiments thereof, relates to the methods for improving pancreatic insulin secretion, thereof to enhance glucose uptake by PRs and other retinal cells. Additionally or alternatively, the invention relates to restoration of transduction of signaling in cone PRs by ONS induced glutamate release. The methods of the invention, in some embodiments thereof, include priming of the retina choroid and optic nerve thereof to enhance the efficacy of cell transplantation therapy. The methods of the invention, in some embodiments thereof, also include identifying a subject prone to or suffering from a disease or condition associated with reduced OBF. Methods of the invention, in some embodiments thereof, may also include monitoring the subject for prophylactic treatment where the patients are at pre-clinical stage of the disease. The OBF of subjects who had received neuromodulation treatment may also be monitored for re-treatment.The present invention, in some embodiments thereof, relates to a method and / or device for treatment of dysregulated reduced blood (e.g. reduced ocular blood flow) and, more particularly, but not exclusively, to methods and / or devices for treatment retinal, choroidal and optic nerve disorders. Optionally, treatment may include application of an effective amount of ONS ophthalmic nerve stimulation alone and / or in combination with peri-ocular administration of substance Neuropeptides / Platelet Rich Plasma (N / PRP) and / or ascorbic acid as a sympatholytic agent

The present disclosure relates to methods for treating plexiform neurofibromas associated with neurofibromatosis type 1 (NF1-PN), comprising administering to a pediatric patient (e.g., 2 to 15 years of age) in need thereof mirdametinib or a pharmaceutically acceptable salt thereof.

The invention discloses a primer and probe composition for detecting neurofibroma type I NF1 gene variation sites, belongs to the technical field of gene diagnosis, and provides a group of specific primers and probe compositions aiming at 12 specific high-frequency or pathogenicity-clear variation sites of an NF1 gene. The composition comprises a specific primer pair aiming at 12 specific high-frequency or specific pathogenicity variation sites of the neurofibroma I-type NF1 gene and a double-labeled oligonucleotide probe matched with the specific primer pair, and the probe is suitable for melting curve analysis; the sequences of the primer pair and the probe of the 12 variation sites are SEQ ID NO. 1 to SEQ ID NO. 36. The primer and probe composition is high in specificity and sensitivity, the kit is easy and convenient to operate and low in cost, the detection result is consistent with that of a gold standard Sanger sequencing method, and the primer and probe composition is suitable for rapid screening and auxiliary diagnosis of clinical samples and has wide clinical application prospects and market value.

In an illustrative embodiment, methods and systems for treating fertility conditions in women diagnosed with polycystic ovary syndrome (PCOS), endometriosis, and / or adenomyosis using electrical neurostimulation include delivering neurostimulation therapy via electrical or mechanical stimulation elements, the neurostimulation therapy including applying first neurostimulation pulses using electrical neurostimulation or mechanical neurostimulation at one or more first regions of skin of the subject to directly and / or indirectly activate a nucleus tractus solitary (NTS) and / or a trigeminal cervical complex (TCC) to activate anti-inflammatory pathways, and applying second neurostimulation pulses using electrical neurostimulation or mechanical neurostimulation at one or more second regions of skin of the subject to directly and / or indirectly activate vagal neural fibers and / or trigeminal neural fibers, wherein the neurostimulation pulses are configured to increase a parasympathetic / sympathetic (P / S) ratio.

The invention belongs to the field of medicines, and particularly relates to application of axitinib in preparation of a medicine for treating plexus neurofibroma. In the medicine, axitinib serves as the only effective component or one of the effective components. When axitinib in the medicine is used as one of the effective components, the effective components further comprise an MEK inhibitor. The MEK inhibitor is one selected from the group consisting of simetinib and trametinib. The invention proves that axitinib can play a role in inhibiting pNF by targeting an important gene OTUD3 for promoting the progress of pNF. Moreover, axitinib is a medicine already used for clinical treatment and is good in safety, and research results show that the neurofibroma inhibition effect can be improved by combined use of axitinib and the MEK inhibitor.