243 results about "L-S DISEASE" patented technology

This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and / or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and / or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.

The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and / or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and / or (3) a nucleic acid sequence encoding (1) or (2). In certain embodiments, the invention provides methods of treating diseases such as Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis using amyotrophic disease-specific epitopes, and compositions including these epitopes. The invention also provides antibodies that bind to monomeric or misfolded SOD1, and not on the molecular surface of native homodimeric SOD1. In addition, the invention includes methods of diagnosing Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis in a subject. Also, the invention provides methods of identifying substances for the treatment or prevention of Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis and kits using the binding proteins of the invention.

This invention is related to carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones represented by Formula I: ##STR1## or a pharmaceutically acceptable salt or prodrug thereof, wherein: Y is oxygen or sulfur; R.sub.1, R.sub.21, R.sub.22 and R.sub.23 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; or R.sub.22 and R.sub.23, together with the N, form a heterocycle; A.sub.1 and A.sub.2 are independently aryl, heteroaryl, saturated or partially unsaturated carbocycle or saturated or partially unsaturated heterocycle, any of which is optionally substituted; X is one or O, S, NR.sub.24, CR.sub.25 R.sub.26, C(O), NR.sub.24 C(O), C(O)NR.sub.24, SO, SO.sub.2 or a covalent bond; where R.sub.24, R.sub.25 and R.sub.26 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl. The invention also is directed to the use of carbocycle and heterocycle substituted semicarbazones and thiosemicarbazones for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), for the treatment and prevention of otoneurotoxicity and eye diseases involving glutamate toxicity and for the treatment, prevention or amelioration of pain, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy and urinary incontinence.

The present invention relates to novel methods for treating dominant gain-of-function diseases. The invention provides methods for targeting regions of the copper zinc superoxide dismutase (SOD1), which causes inherited amyotrophic lateral sclerosis (ALS), with RNAi agent. The invention further provides RNAi resistant replacement genes containing mismatches with their respective RNAi agents. The invention also provides for vectors that express RNAi agent and RNAi resistant replacement gene of the present invention.

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 4-(p-quinolyl)-2-hydroxybutanamide derivatives. Methods and compounds useful in treating other disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, Parkinson's disease, and pervasive developmental disorders such as autism are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.

The present invention relates to the use of creatine compound and neuroprotective combinations including creatine, creatine phosphate or analogs of creatine, such as cyclocreatine, for treating diseases of the nervous system. Creatine compounds in combination with neuroprotective agents can be used as therapeutically effective compositions against a variety of diseases of the nervous system such as diabetic and toxic neuropathies, peripheral nervous system diseases, Alzheimer disease, Parkinson's disease, stroke, Huntington's disease, amyotropic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, dysmyelination and demyelination disorders, and mitochondrial diseases. The creatine compounds which can be used in the present method include (1) creatine, creatine phosphate and analogs of these compounds which can act as substrates or substrate analogs for creatine kinase; (2) bisubstrate inhibitors of creatine kinase comprising covalently linked structural analogs of adenosine triphosphate (ATP) and creatine; (3) creatine analogs which can act as reversible or irreversible inhibitors of creatine kinase; and (4) N-phosphorocreatine analogs bearing non-transferable moieties which mimic the N-phosphoryl group.

The present application is directed to therapeutic compounds, compositions, and methods for culturing neuronal cells and for preventing and the treatment of neurodegenerative diseases, such as Parkinson's disease and amyotrophic lateral sclerosis (ALS).

The invention provides a method for diagnosing amyotrophic lateral sclerosis (ALS) in a subject, a method for assessing the effectiveness of a drug in treating ALS, and a method for determining the site of onset of ALS in a subject. Each method comprises (a) obtaining a sample from the subject, (b) analyzing the proteins in the sample by mass spectroscopy, and (c) determining a mass spectral profile for the sample. In some embodiments, the method comprises comparing the mass spectral profile of the sample to the mass spectral profile of a positive or a negative standard.

A method for treating amyotrophic lateral sclerosis (ALS) in a human subject is provided. A first vibration stimulation member is introduced into a posterior part of a first nasal cavity of the human subject. By means of the first vibration stimulation member, vibrations are imparted to the posterior part of the first nasal cavity at frequency in a range of from 60 to 70 Hz. A second vibration simulation member is arranged between the trapezius muscle and the sternocleidomastoid muscle on a first side of the neck of the human subject; and by means of said second vibration stimulation member, vibrations are imparted to the first side of the neck at a frequency in a range of from 30 to 50 Hz.

The invention provides a method for determining the onset and / or progression of ALS in an animal. The method comprises (a) obtaining a sample from the animal, (b) analyzing the proteins in the sample by mass spectroscopy, and (c) determining a mass spectral profile for the sample. The invention also provides isolated protein biomarkers of ALS.

A composition for administration to a subject, such as oral administration to a subject, for example, has been provided. Such a composition may comprise at least one magnesium-counter ion compound. A magnesium-counter ion composition described herein may be useful for any of a variety of applications provided herein, such as maintaining, enhancing, and / or improving health, nutrition, and / or another condition of a subject, and / or cognitive, learning, and / or memory function. A magnesium-counter ion composition provided herein may be useful for administration to a subject presenting magnesium deficiency, mild cognitive impairment, Alzheimer's disease, attention deficit hyperactivity disorder, ALS, Parkinson's disease, diabetes, migraine, anxiety disorder, mood disorder, and / or hypertension. A kit, method, and other associated technology are also provided.

The present invention provides methods and compositions for modulating polyamine pathway activity as a means for ameliorating neurodegenarative disorders. In particular, for ameliorating the symptoms or onset of amyotrophic lateral sclerosis (ALS) by modulating the gene and protein products involved the polyamine pathway, such as by inhibiting the enzyme, ornithine decarboxylase (ODC), involved in the synthesis of the polyamine, putrescine. Compositions and methods are disclosed for inhibiting the polyamine pathway producing lower polyamine levels resulting in a beneficial effect on ALS. This can be accomplished by using modulating agents such as analogs, or polyamine analogs, and antiproliferative drugs. Screening assays for pharmacological agents that are capable of decreasing polyamine levels and / or reducing cell proliferation are also disclosed.

Disclosed are conjugates of Abeta-binding peptides and CsA analogs and conjugates of Abeta-binding peptides and FK506 Binding Peptide inhibitors. These conjugates chemically induce dimerization of either cyclophilin or FK506 Binding Peptide with Abeta peptide, a major component of amyloid plaques found in neurological disorders such as Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis. The conjugates are useful in the treatment of neurological diseases involving the formation of amyloid plaques because they inhibit and / or prevent the aggregation and deposition of Abeta peptide into plaques.

The present invention provides biomarkers and diagnostic methods employing such biomarkers based on the discovery of genes that have a two-fold or greater difference in gene expression in the spinal cord of a pre-symptomatic mouse model of amyotrophic lateral sclerosis. Such biomarkers and diagnostic methods are useful for early detection of neural cell injury and death in acute and degenerative disease.

The disclosure relates to oligomers capable of targeting RNA expressed from the human C9ORF72 gene containing a pathogenic hexanucleotide repeat expansion. Such oligomers are useful for, among other things, reducing or eliminating C9ORF72 RNA and / or proteins translated therefrom, and treating or preventing diseases or disorders caused by, or associated with, hexanucleotide repeat expansion, including familial frontotemporal dementia (FTD) and familial amyotrophic lateral sclerosis (ALS).

A method for treating patients with Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease. In accordance with the method of treatment, transcranial AC pulsed electromagnetic fields (EMFs) in substantially square waveforms in particular frequency and amplitude ranges and picotesla quantities are applied to the patient's brain. EMFs are applied via a transducer array containing a plurality of flexible circular coils in an arrangement placed over the scalp of an ALS patient. The treatment method ameliorates symptoms associated with the disease state and slows the progression of the disease.

Provided herein are methods of treatment of Amyotrophic Lateral Sclerosis comprising administration of adrenocorticotropic hormone (ACTH), or fragment, analog, complex or aggregate thereof, or any combination thereof, to an individual in need thereof.

The invention relates to an assay for discriminating between amyotrophic lateral sclerosis (ALS) patients and patients with ALS-like disorders that express symptoms like ALS. The method is based on the use of 2-dimensional (2D) gel electrophoresis to separate the complex mixture of proteins found in blood serum, the quantitation of a group of identified biomarkers, and the biostatistical analysis of the concentration of the identified biomarkers to differentiate patients having ALS from patients having other ALS-like disorders.

A Chinese medicine for treating the myophagism and myasthenia gravis caused by motor neuron diseases, prograssive myodystrophy and congenital myopathy is prepared from ginseng and epimedium. Its preparing process is also disclosed.

8′-Hydroxy-Dihydroergotamine (8′-OH DHE) medicinal compounds, compositions, and dosage forms containing such compositions are provided. Also provided herein are methods of treatment, prevention, or amelioration of diseases, conditions or disorders selected from amyotrophic lateral sclerosis (ALS), Parkinson's disease, stress / anxiety, nausea, emesis, aggression, pain, neuropathic pain, sleeplessness, insomnia, restless leg syndrome and depression using the compounds, compositions, dosage forms and administration techniques disclosed herein.

The invention relates to an epitope protection assay for use in diagnosis, prognosis and therapeutic intervention in diseases, for example, involving polypeptide aggregation, such as prion infections. The methods of the invention first block accessible polypeptide target epitope with a blocking agent. After denaturation of the polypeptide, a detecting agent is used to detect protein with target epitope that was inaccessible during contact with the blocking agent. The invention also relates to novel amyotrophic lateral sclerosis-specific epitopes and their uses to make antibodies, and to the novel antibodies and uses thereof.

Provided is a composition for treating nerve damage-related diseases. The composition includes a human umbilical cord blood-derived mesenchymal stem cell as an active ingredient. The mesenchymal stem cell isolated and incubated from the human umbilical cord blood migrates to an injured area to be differentiated into a nerve cell or a neuroglial cell at the time of in vivo transplantation. Thus, the mesenchymal stem cell and a composition including the same can be effectively used in cell replacement therapy and gene therapy for treating diseases caused by nerve damage including a stroke, Parkinson's disease, Alzheimer's disease, Pick's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic central nervous system disease and a spinal cord injury.

This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors, R-isomers, and non-hydroxylated and / or non-chiral propanamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

The present invention relates to compositions and methods for the treatment of amyotrophic lateral sclerosis. More specifically, the present invention relates to novel combinatorial therapies for treating amyotrophic lateral sclerosis or a related disorder.

This invention provides novel indole, indazole, benzimidazole, indoline, quinolone, isoquinoline, and carbazole selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyper androgenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic and / or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

The present invention relates to neurological and physiological dysfunction associated with neuron disorders. In (particular, the invention relates to the involvement of vascular endothelial growth factor (VEGF) and homologues in the aetiology of motor neuron disorders. The invention further concerns a novel, mutant transgenic mouse (VEGFm / m) with a homozygous deletion in the hypoxia responsive element (HRE) of the VEGF promoter which alters the hypoxic upregulation of VEGF. These mice suffer severe adult onset muscle weakness due to progressive spinal motor neuron degeneration which is reminiscent of amyotrophic lateral sclerosis (ALS)-a fatal disorder with unknown aetiology. Furthermore, the neuropathy of these mice is not caused by vascular defects, but is due to defective VEGF-mediated survival signals to motor neurons. The present invention relates in particular to the isoform VEGF165 which stimulates survival of motor neurons via binding to neuropilin-1, a receptor known to bind semaphorin-3A which is implicated in axon retraction and neuronal death, and the VEGF Receptor-2. The present invention thus relates to the usage of VEGF, in particular VEGF165, for the treatment of neuron disorders and relates, in addition, to the usage of polymorphisms in the VEGF promotor for diagnosing the latter disorders.

The present invention relates to monoclonal anti-Sortilin antibodies which have been found useful in correcting a deficient level of progranulin (PGRN). In particular, these antibodies can be used in the treatment of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders such as Alzheimers disease (AD).

The invention pertains to the field of traditional Chinese medicine, in particular to a medicine preparation for treating amyotrophic lateral sclerosis and a preparation method thereof. The medicine preparation adopts the treatment principles of benefiting qi, nourishing yin and reinforcing yang, the traditional Chinese medicine compound preparation is prepared by taking pharmaceutical raw materials of membranous milkvetch root, dried rehmannia root, epimedium herb, medicinal Indianmulberry root and common macrocarpium fruit; the clinical studies show that the medicine preparation can significantly reduce the clinical integral of the traditional Chinese medicine symptoms of flaccidity diseases and improve the clinical symptoms of the patients with the flaccidity diseases / ALS; compared with the prior art, the treatment effects are significantly improved, furthermore, the medicine preparation is safe, reliable and has no nausea, vomit, decreased appetite, abdominal distension or other evident common side effects of riluzole.

The invention discloses a genetic genetic diagnosis kit for amyotrophic lateral sclerosis. The kit and a detection method are characterized in that gene-specific primers are designed and synthesized according to a virulence gene which is studied and reported to be correlated with the amyotrophic lateral sclerosis, including SOD1, FUS, VAPB, ANG, TARDBP, FIG4, OPTN, VCP, Sigmar1, CHMP2B and PFN1 sites, a sample is obtained from an individual to be detected, a RT-PCR technology is carried out, the RT-PCR product is subjected to sequencing analysis, next, the sample sequence is compared with a normal gene sequence to determine whether the sample sequence has disease-causing mutations. The kit is capable of detecting all disease-causing mutation sites of the coding sequence (CDS) of the virulence gene at a time, and has the advantages of being simple and quick, reliable in preparation, good in specificity, high in sensitivity and the like; the kit is capable of detecting the ALS patients and asymptomatic patients.