Amicus Therapeutics, Inc.

Transcriptx, Inc.

Amacus Therapeutics, Inc.

Brandon Alan Wustman

John R Flanagan

Elfrida Benjamin

Hung V Do

Xiaoyang Wu

David J Lockhart

Mirko Hennig

Daniella Ishimaru

Robert E Boyd

Kenneth Valenzano

Polynucleotides encoding peptides, proteins, enzymes, and functional fragments thereof are disclosed. The polynucleotides of the disclosure can be effectively delivered to an organ, such as the lung, and expressed within cells of the organ. The polyribonucleotides of the disclosure can be used to treat a disease or condition associated with cilia maintenance and function, impaired function of the axoneme, such as DNAI1 or DNAH5.

Treatment of primary ciliary dyskinesia with synthetic messenger RNA

The present invention provides methods to determine whether a patient with a lysosomal storage disorder will benefit from treatment with a specific pharmacological chaperone. The present invention exemplifies an in vitro method for determining &#x3b1;-galactosidase A responsiveness to a pharmacological chaperone such as 1-deoxygalactonojirimycin in a cell line expressing a mutant from of &#x3b1;-galactosidase A. The invention also provides a method for diagnosing Fabry disease in patients suspected of having Fabry disease.

Method to predict response to pharmacological chaperone treatment of diseases

Provided is a method of increasing the stability of wild-type &#x3b2;-glucocerebrosidase. Also provided are methods of treating and/or preventing an individual having a neurological disease in which increased expression or activity of &#x3b2;-glucocerebrosidase in the central nervous system would be beneficial. This method comprises administering an effective amount of a pharmacologic chaperone for &#x3b2;-glucocerebrosidase, with the proviso that the individual does not have a mutation in the gene encoding &#x3b2;-glucocerebrosidase. Further provided are &#x3b2;-glucocerebrosidase inhibitors which have been identified as specific pharmacologic chaperones and which have been shown to increase activity of &#x3b2;-glucocerebrosidase in vivo in the central nervous system.

Method for the treatment of neurological disorders by enhancing the activity of &#x3b2;-glucocerebrosidase

The present invention relates to a method for treating an individual having Cerebral Amyloid Angiopathy by using pharmacological chaperones to increase the activity of gangliosidase and/or sialidase enzymes involved in ganglioside catabolism.

Method for treating cerebral amyloid angiopathy using pharmacological chaperones to increase the activity of gangliosidases

Described herein are dosing regimens and kits for the treatment and/or prevention of cerebral amyloidoses such as Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA).

Dosing regimens for treating and/or preventing cerebral amyloidoses

Described is a method for treating an individual having a neurological disorder with an associated mutation or mutations in a gene encoding a lysosomal enzyme. Specifically, the individual is administered a specific pharmacological chaperone for the lysosomal enzyme which increases trafficking of the protein from the ER to the lysosome in neural cells, with or without concomitantly increasing enzyme activity in neural cells. Restoration of trafficking relieves cell stress and other toxicities associated with accumulation of mutant proteins. Restoration of enzyme activity relieves substrate accumulation and pathologies associated with lipid accumulation. In a specific embodiment, the neurological disorder is Parkinson's disease or parkinsonism which is associated with mutations in glucocerebrosidase.

Treatment of CNS disorders associated with mutations in genes encoding lysosomal enzymes

Provided is a method of increasing the stability of wild-type &#x3b2;-glucocerebrosidase. Also provided are methods of treating and/or preventing an individual having a neurological disease in which increased expression or activity of &#x3b2;-glucocerebrosidase in the central nervous system would be beneficial. This method includes administering an effective amount of a pharmacologic chaperone for &#x3b2;-glucocerebrosidase, with the proviso that the individual does not have a mutation in the gene encoding &#x3b2;-glucocerebrosidase. Further provided are &#x3b2;-glucocerebrosidase inhibitors which have been identified as specific pharmacologic chaperones and which have been shown to increase activity of &#x3b2;-glucocerebrosidase in vivo in the central nervous system.

Method for the treatment of neurological disorders by enhancing the activity of beta-glucocerebrosidase

The present invention provides methods to determine whether a patient with a lysosomal storage disorder win benefit from treatment with a specific pharmacological chaperone. The present invention exemplifies an in vitro method for determining &#x3b1;-galactosidase A responsiveness to a pharmacological chaperone such as 1-deoxygalactonojirimycin in a cell line expressing a mutant from of &#x3b1;-galactosidase A. The invention also provides a method for diagnosing Fabry disease in patients suspected of having Fabry disease.

The present invention provides dosing regimens for administering pharmacological chaperones to a subject in need thereof. The dosing regimens can be used to treat disorders caused by improper protein misfolding, such as lysosomal storage disorders.

Dosing regimens for the treatment of lysosomal storage diseases using pharmacological chaperones

The present invention relates to a method for treating an individual having Alzheimer's Disease by using pharmacological chaperones to increase the activity of gangliosidase and/or sialidase enzymes involved in ganglioside catabolism.

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San Diego, CA, United States of America

Brandon Alan Wustman