84 results about "Synucleinopathies" patented technology

This invention provides specifically substituted 1,2,4-thiadiazole derivatives for use in the treatment of an α-synucleopathy such as Parkinson's disease, diffuse Lewy body disease, traumatic brain injury, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy and Alzheimer's disease. This invention also provides various methods for producing such substituted 1,2,4-thiadiazole derivatives.

Antibodies and fragments thereof have high affinity for human α-synuclein protofibrils and low binding of α-synuclein monomers, wherein the antibodies or fragments have specified Complementarity Determining Region (CDR) sequences. Compositions comprise such an antibody or fragment and methods of detecting α-synuclein protofibrils use such an antibody or fragment. In further embodiments, methods of preventing, delaying onset of or treating a neurodegenerative disorder with α-synuclein pathology comprise administering such an antibody or fragment, and such an antibody or fragment is used in the manufacture of a pharmaceutical composition for treatment of a neurodegenerative disorder with α-synuclein pathology. Such an antibody or fragment is used in the diagnosis or monitoring of the development of a neurodegenerative disorder with α-synuclein pathology, and in methods for reducing or inhibiting α-synuclein aggregation by administration of such an antibody or fragment.

Dihydroxyaryl compounds and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of β-amyloid diseases, such as observed in Alzheimer's disease, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

The present invention generally relates to various compounds that are useful as α-synuclein ligands. The invention further relates to methods of using these compounds and their radiolabeled analogs for the detection of synucleinopathies, including Parkinson's disease (PD).

This invention provides thiazolylpiperazine derivatives, and N-sulfonyl heterocyclic derivatives including phenyl- and benzyl-thiazolylpiperidine derivatives, and pharmaceutically acceptable salts thereof, which are useful active ingredients for administration in a method for the treatment of an α-synucleopathy such as Parkinson's disease, diffuse Lewy body disease, traumatic brain injury, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy and Alzheimer's disease. This invention also provides methods for making such derivatives, and pharmaceutical compositions including such derivatives together with pharmaceutically acceptable excipients.

Derivatives of phenothiazine, phenoxazine, and phenazine compounds and their use as α-synuclein ligands are described. Also described are methods of using these compounds and their radiolabeled analogs for the detection, monitoring, and treatment of synucleinopathies, including Parkinson's disease.

Present inventions demonstrates that alpha synuclein toxicity such as α-synuclein mediated cell death, alpha synuclein induced reactive oxygen species (ROS) in a cell requires the proapoptotic endonuclease G and that the deletion of the endonuclease G or suppressing of the endonuclease G apoptotic pathway attenuates or counteracts such alpha synuclein toxicity. The present invention compositions and methods for inhibition of α-synuclein toxicity. The inhibiting α-synuclein toxicity can be used in methods of treatment of synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), pure autonomic failure (PAF), and multiple system atrophy (MSA) and the manufacture of medicaments for such treatment. In particular The subject matter provided in herein relates to a pharmaceutical compositions containing inhibitors of endonuclease G, and their use in the treatment of synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies, pure autonomic failure, and multiple system atrophy and the manufacture of medicaments for such treatment. Furthermore the present invention relates to a method for the identification of compounds attenuating the synuclein toxicity, said method comprising evaluating the inhibitory action of said compound on the endonuclease G dependent apoptosis.

The present invention generally relates to various compounds that are useful as α-synuclein ligands. The invention further relates to methods of using these compounds and their radiolabeled analogs for the detection of synucleinopathies, including Parkinson's disease (PD).

Novel quinolinone farnesyl transferase inhibitors are provided. These new compounds are useful in the treatment or prevention of synucleinopathies, such as Parkinson's Disease, Diffuse Lewy Body Disease, multiple system atrophy, and disorders of brain iron concentration including pantothenate kinase-associated neurodegeneration (e.g., PANK1), or other neurodegenerative/neurological diseases. Provided compounds are also useful in the treatment of proliferative diseases such as cancer, and in the treatment of neurological diseases, such as cognitive impairment, depression, and anxiety.

The treatment including administering to a subject a therapeutically effective amount of an inventive farnesyl transferase inhibitor compound.

Dihydroxyaryl compounds and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

Provided is a method for treatment or prevention of α-synucleinopathies in a mammalian subject, the method comprising administering a therapeutically effective amount of at least one composition to the subject, wherein the composition comprises a molecule for pharmacological modulation of galectin activity in a mammalian brain.

A method of detecting alpha-synuclein in a sample of a subject comprising the steps of a) Obtaining a sample from a subject,5 b) Applying the sample on a luminescence assay, and c) Optionally, comparing the results with a control

A method of detecting the presence of alpha-synuclein aggregation in a biological sample is provided whereby a biological sample is mixed with a reaction sample comprising a population of beads, a fluorophore adapted to bind to protein aggregates and to increase fluorescence when bound to protein aggregates, and alpha-synuclein or a fragment or variant thereof to form a reaction mixture, the reaction mixture is illuminated and at the same time incubated with intermittent agitation cycles, wherein a significant increase in the fluorescence of the reaction mixture during incubation is indicative of the presence of aggregates of alpha-synuclein in the biological sample. Method of diagnosing alpha-synucleinopathies such as Parkinson's disease or Dementia with Lewy Bodies.

The application is directed to compounds of formula (I): and their salts and solvates, wherein R¹, R², R³, A¹, A², A³, and n are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of a lysosomal storage disease, such as Gaucher's, and other diseases or disorders that are synucleinopathies.