29 results about "SOD1" patented technology

The present application relates to siRNA and oligonucleotide agents for use in the prevention or treatment of SOD1-related neurodegenerative diseases or conditions, such as amyotrophic lateral sclerosis, ALS. The oligonucleotide agent comprises a double-stranded targeting oligonucleotide (siRNA) and a non-targeting single-stranded oligonucleotide (ACO), wherein the siRNA targets the mRNA region of the target gene SOD1.

Provided herein are SOD1 RNAi agents and compositions comprising a SOD1 RNAi agent. Also provided herein are methods of using the SOD1 RNAi agents or compositions comprising a SOD1 RNAi agent in reducing SOD1 expression and / or treating SOD1-mediated neurological disease.

In some aspects, the disclosure relates to compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject). In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a hardened SOD1 protein. In some embodiments, compositions and methods described by the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.

The invention discloses a construction method and application of a zebra fish model. The construction method comprises the following steps: taking zebra fish as a model animal, and obtaining a zebra fish model by knocking out a sod1 gene in the zebra fish and / or expressing a human source sod1 gene mutant in the zebra fish; wherein the serial number of the sod1 gene in the zebra fish in an Ensepbl database is ENSDARG00000043848, and the nucleotide sequence of the human source sod1 gene mutant is as shown in SEQ ID NO. 1. The zebrafish can be used for the function research of the sod1 gene in the zebrafish, the function research of the human-derived sod1 gene mutant, the pathological research of amyotrophic lateral sclerosis and the screening of amyotrophic lateral sclerosis resisting drugs.

Antibody or binding fragment thereof, fusion protein, or pharmaceutical composition directed against misfolded SOD1 epitope, or nucleic acid encoding the antibody or binding fragment thereof, fusion protein, or pharmaceutical composition, are described. Also provided are methods for using and manufacturing such antibody or binding fragment thereof, fusion protein, nucleic acid, or pharmaceutical composition, as well as methods of their use for treating a disorder in a human subject in need thereof.

To provide compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject).SOLUTION: In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a reinforced SOD1 protein. In some embodiments, compositions and methods described in the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.SELECTED DRAWING: Figure 1

Abstract Dosage regimens for SOD1-targeting antisense oligonucleotides, and salts thereof, are provided. These dosage regimens find use in the treatment of subjects having or at risk of developing amyotrophic lateral sclerosis. Abstract 20 26 20 53 14 06 J ul 2 02 6 A b s t r a c t 2 0 2 6 2 0 5 3 1 4 0 6 J u l 2 0 2 6

The invention relates to the technical field of protein, in particular to a preparation method and application of deep-deep-derived grease-resistant low-temperature superoxide dismutase SOD1. Through rational design or high-throughput screening, the SOD1 variant which keeps high activity in a grease environment and is sensitive to temperature is obtained, and the sequence is as shown in SEQ ID NO: 6. The enzyme can be widely applied to the technical fields of food preservation, skin care products, grease oxidation resistance and low-temperature biology, and the key defects of existing SOD1 in industrial application are overcome.

The present invention is directed to a pharmaceutical composition and method for treating a subj ect diagnosed amyotrophic lateral sclerosis (ALS) with a pharmaceutical composition containing dissolved or dispersed therein a SOD1 and / or TDP-43 aggregation- inhibiting amount of a rose bengal (RB) compound that is a pharmaceutically acceptable salt of RB, RB lactone, a RB amide, an aromatic RB derivative, wherein the aromatic derivative is an ester or amide formed from an alcohol or monosubstituted amine having a 5 - or 6 -membered aromatic ring, or a 5, 6 - or 6, 6 - fused aromatic ring system that contains 0, 1, or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur. This treatment method is typically repeated a plurality of times or until the subj ect no longer needs it.

Aspects of this disclosure provide compounds, compositions, and methods for regulating the expression or activity of superoxide dismutase 1 (SOD1). In some aspects, the compounds, compositions, and methods of this disclosure can be used to reduce the expression of SOD1 mRNA in cells or animals. In some aspects, the compounds, compositions, and methods of this disclosure can be used to reduce the expression of SOD1 protein in cells or animals. In certain embodiments, the animal has a CNS-related disease, disorder, or condition.

This invention relates to the field of bioactive peptide technology, and discloses a tetrapeptide with cognitive-improving function and its applications. The primary amino acid sequence of the tetrapeptide is Lys-Gly-Phe-Pro, and its molecular weight is 489.2587 Da. The tetrapeptide of this invention can be chemically synthesized or directionally prepared from sea cucumber protease hydrolysates. The tetrapeptide of this invention exhibits cognitive-improving activity, mainly through inhibiting GABA. B The expression of R activates the cAMP / PKA / CREB signaling pathway, promotes the release of the inhibitory neurotransmitter GABA, reduces oxidative stress damage, increases the gene expression of neurotrophic factors Bdnf and Nt3, and significantly upregulates the gene expression of antioxidant enzymes Sod1 and Gpx1, thereby exerting a neuroprotective effect and improving age-induced cognitive impairment.

The present invention is directed to a pharmaceutical composition and method for treating a subject diagnosed amyotrophic lateral sclerosis (ALS) with a pharmaceutical composition containing dissolved or dispersed therein a SOD1 and / or TDP-43 aggregation-inhibiting amount of a rose bengal (RB) compound that is a pharmaceutically acceptable salt of RB, RB lactone, a RB amide, an aromatic RB derivative, wherein the aromatic derivative is an ester or amide formed from an alcohol or monosubstituted amine having a 5- or 6-membered aromatic ring, or a 5,6- or 6,6-fused aromatic ring system that contains 0, 1, or 2 hetero ring atoms that are independently nitrogen, oxygen or sulfur. This treatment method is typically repeated a plurality of times or until the subject no longer needs it.

Use of a protein polymer in the treatment of amyotrophic lateral sclerosis. The protein polymer is obtained by stimulating and subsequently lysing mesenchymal stem cells, followed by isolation and purification. In SOD1 mutant mouse experiments, the protein polymer can significantly increase the number of motor neurons in the spinal anterior horn, ameliorate muscle atrophy, improve the motor ability of mice, and prolong the survival time of mice. In clinical trials, the protein polymer exhibits the effect of blocking the progression of amyotrophic lateral sclerosis, can reduce the concentration of TDP-43 protein in cerebrospinal fluid, and can increase the concentration of TDP-43 protein in serum.

The present disclosure features compositions and methods for treating a condition associated with the expression of a wild-type or mutant superoxide dismutase 1 (SOD1) RNA transcript, which can result in a pathological phenotype. Disclosed herein are inhibitory RNA constructs that inhibit the expression of SOD1, as well as viral vectors, such as adeno-associated viral vectors, encoding such inhibitory RNA molecules.

The present invention relates to a use of a novel compound, for preventing, improving or treating amyotrophic lateral sclerosis (ALS), wherein the present inventors have found that SOD1 aggregation is one of the important causes of ALS, and have proposed the possibility that WT-SOD1 aggregation, caused by suppressing the regulation of intracellular stress or TDP-43, may be a cause of sALS. In addition, the present inventors have discovered the novel compound PRG-A-01(SLC-B036) as a SOD1 aggregation and misfolding inhibitor.

To solve the problem of the lack of biomarkers that facilitate early diagnosis, demonstrate target binding, monitor disease progression, and / or can serve as surrogate end points for evaluating the efficacy of treatment.SOLUTION: Provided is a novel high-sensitivity method for assaying misfolded SOD1 in a body fluid of a subject, particularly in cerebrospinal fluid. The method is based on a novel high-sensitivity immunoassay utilizing a unique epitope of SOD1 and a corresponding anti-SOD1 antibody. In addition, a kit containing the components of an immunoassay is provided.SELECTED DRAWING: None

Aspects of the disclosure relate to compositions and methods for reducing expression or activity of superoxide dismutase 1 (SOD1) in a cell or subject. In some embodiments, the compositions, such as nucleic acid and viral vectors, comprise artificial microRNAs (amiRNAs) having a SOD1-targeting sequence positioned within a microRNA scaffold. In some embodiments, the compositions further comprise a human SMN1 promoter. In some aspects, the methods comprise administering a composition of the disclosure to a subject, for example a subject having amyotrophic lateral sclerosis (ALS).

The present invention relates to a method for in vitro diagnosis of Long COVID in a subject, wherein the method comprises the following steps: a) providing a biological sample obtained from the subject; b) measuring the levels of at least one protein in said sample, wherein the at least one protein is selected from Autophagy Related 4B Cysteine Peptidase (ATG4B), Mitofusin 2 (MFN2), Dynamin-related Protein 1 (DRP1), and / or Superoxide dismutase 1 (SOD1); and c) comparing the levels of the at least one protein measured in step b) with a respective reference, wherein an increase in the levels of the at least one protein in said sample relative to the reference is indicative of Long COVID diagnosis.

It relates to a method for the treatment of famyotrophic lateral sclerosis (ALS) by an oligonucleotide agent, comprising the step of administering the subject a treatment effective amount of the oligonucleotide agent, wherein the oligonucleotide agent comprises a double-stranded targeting oligonucleotide (siRNA) and a non-targeting single-stranded accessory oligonucleotide (ACO). The method can be used in the treatment of ALS with and without SOD1 mutation. It also provides a safety therapeutic window and an effective dosing regimen for the treatment of ALS using the oligonucleotide agent.

The present disclosure provides oligonucleotides, pharmaceutical compositions, kits, and methods of using the oligonucleotide. The oligonucleotides comprise a central nervous system (CNS) ligand. A strand of the oligonucleotides may be a therapeutic or prophylactic agent. The oligonucleotides may be able to deliver the therapeutic or prophylactic agent to a subject. The oligonucleotides may be useful in modulate (e.g., inhibiting) the expression or activity of superoxide dismutase 1 (SOD1) and in treating or preventing diseases, e.g., central nervous system (CNS) diseases, in the subject.

The present invention relates to a use of a novel compound, for preventing, improving or treating amyotrophic lateral sclerosis (ALS). The present inventors have found that SOD1 aggregation is one of the important causes of ALS, and have proposed the possibility that WT-SOD1 aggregation, caused by suppressing the regulation of intracellular stress or TDP-43, may be a cause of sALS. In addition, the present inventors have discovered the novel compound PRG-A-01 (SLC-B036) as a SOD1 aggregation and misfolding inhibitor. The compound exhibited a protective effect against muscle weakness and movement disorder in an ALS mouse model. According to the result of a histological analysis, intraspinal nerves were maintained by means of a treatment using PRG-A-01 (SLC-B036). In addition, the present inventors have obtained a candidate compound (PRG-A-04) which can be a more optimized drug. Consequently, the compound of the present invention may be usefully employed in developing a therapeutic agent for ALS.

The invention is applicable to the technical field of biological medicines, and provides application of lisinopril in preparation of a medicine for treating amyotrophic lateral sclerosis. The invention has important value for promoting research and development of amyotrophic lateral sclerosis (ALS) treatment medicines and improving prognosis of patients. In-vitro experiments show that lisinopril can prevent mitochondria damage of NSC34 cells induced by SOD1G93A, expression of Beclin 1, LC3 and p62 is regulated by inhibiting a TGF [beta] 1 / PI3K / AKT / mTOR signal channel, cell autophagy is activated, and neuronal apoptosis is inhibited. In-vivo experiments show that lisinopril can activate in-vivo BI1 expression, regulate ALS model mouse lipid content and intervene in a glycerophospholipid metabolic process, and also can inhibit motor neuron death, myelin sheath shedding and neuromuscular junction degeneration and promote mitochondrial biogenesis by influencing autophagy regulated by a TGF [beta] 1 / PI3K / AKT / mTOR pathway.

The invention relates to the technical field of biological medicine, and discloses a cell-penetrating CPP-SOD1 compound and application thereof in relieving cisplatin-induced renal toxicity, the cell-penetrating CPP-SOD1 compound comprises the following components: a cell-penetrating peptide, the amino acid sequence of the CPP is selected from at least one of TAT, Penetratin or polyarginine, and the amino acid sequence of the SOD1 is selected from at least one of TAT, Penetratin or polyarginine; the amino acid sequence of the superoxide dismutase 1 is as shown in SEQ ID NO: 1; the ROS sensitive connecting peptide is used for connecting the CPP and the SOD1, and the sequence of the connecting peptide comprises a thioketal bond or a matrix metalloproteinase cleavage site; wherein the transmembrane efficiency of the compound is greater than or equal to 70%, the SOD1 activity retention rate is greater than or equal to 85%, and the compound is used for preventing or relieving renal tubular epithelial cell oxidative damage caused by cisplatin chemotherapy. According to the invention, pathological response release is realized by dynamically screening the kidney-targeted cell-penetrating peptide and combining with the ROS sensitive connecting peptide, cell penetrating and enzyme activity are optimized by using two parameters, and delivery-release is tracked based on FRET, so that the problems of poor cell penetrating property and insufficient activity retention are solved, and the renal toxicity protection curative effect of cis-platinum is improved.

The present disclosure provides oligonucleotides, pharmaceutical compositions, kits, and methods of using the oligonucleotide. The oligonucleotides comprise a central nervous system (CNS) ligand. A strand of the oligonucleotides may be a therapeutic or prophylactic agent. The oligonucleotides may be able to deliver the therapeutic or prophylactic agent to a subject. The oligonucleotides may be useful in modulate (e.g., inhibiting) the expression or activity of superoxide dismutase 1 (SOD1) and in treating or preventing diseases, e.g., central nervous system (CNS) diseases, in the subject.

The present invention relates to antisense oligonucleotides that are complimentary to SOD1, leading to decreased expression of SOD1. Reduced expression of SOD1 is beneficial in medical disorders such as Amyotrophic Lateral Sclerosis.

Provided are labeled antibody conjugates for use in methods of diagnosing ALS or monitoring ALS drug therapy and / or progression by immunoimaging in vivo detection and tracking of misfolded SOD1 in a subject, compositions and kits comprising the conjugates, and methods of using these conjugates for in vivo immunoimaging of superoxide dismutase (SOD1) that are used as markers of the efficacy of amyotrophic lateral sclerosis (ALS) or ALS drug treatment of a subject. Furthermore, SOD1 antibodies specific for misfolded and / or aggregated SOD1 are provided for use in the treatment of bone and / or joint related diseases.

The invention belongs to the technical field of medical biology, and particularly relates to an ALS mouse model constructed based on Sptlc-E260K point mutation and a construction method and application of the ALS mouse model. According to the Sptlc2-E260K point mutation mouse, key enzyme SPTLC2 is synthesized through targeted sphingolipid, functional mutation E260K is directly introduced, a sphingolipid metabolism pathway is abnormal, and the core pathology of sphingolipid metabolism imbalance in children type ALS is accurately simulated. Compared with SOD1 and TDP43 models, the invention fills up the blank of the existing model in the study of ALS related to sphingolipid metabolism, and provides a specific tool for exploring a neurodegenerative mechanism driven by abnormal metabolism. The method has the advantages that efficient identification is realized through selection of SPTLC2 gene targets and introduction of codon replacement and restriction enzyme cutting sites, so that the problem of incomplete pathological coverage caused by limitation of gene functions in the prior art is solved.

The invention discloses application of an antioxidant in preparation of a medicine for treating fat infiltration and fibrosis related diseases after rotator cuff injury, and belongs to the technical field of medicines. SD rat rotator cuff injury model research finds that vitamin C and N-acetylcysteine have dual core effects after rotator cuff injury: 1, muscle fiber atrophy, fibrosis hyperplasia and local inflammatory response of skeletal muscle after injury are improved, and muscle fat infiltration is remarkably inhibited; 2, the anti-oxidation defense capability of the body is enhanced, the expression of antioxidant genes such as superoxide dismutase (SOD1, SOD2 and SOD3) and peroxide reductase (PRDX5) is promoted, the activity of antioxidant enzyme is improved, and the oxidative stress level is effectively relieved. The antioxidant provided by the invention can simultaneously improve fat infiltration, fibrosis, muscle atrophy and local chronic inflammation after rotator cuff injury and regulate oxidative stress, is expected to reduce the risk of postoperative retearing and promote functional recovery, and has a wide application prospect.

Aspects of the present disclosure provide compounds, compositions and methods for modulating the expression or activity of superoxide dismutase 1 (SOD1). In some aspects, the compounds, compositions, and methods of the present disclosure are useful for reducing the expression of SOD1 mRNA in a cell or animal. In some aspects, the compounds, compositions, and methods of the present disclosure are useful for reducing the expression of SOD1 protein in a cell or animal.