22 results about "Frataxin" patented technology

The present disclosure relates to compositions and methods for altering, e.g., enhancing, the level of ataxin via delivery of adeno-associated virus (AAV) capsid variants. The compositions and methods of the present disclosure are useful for treating subjects suffering from, having been diagnosed with, or at risk of suffering from a disorder associated with inadequate ataxia, such as Friedel-type ataxia.

The present invention provides gene therapies for the treatment of Friedreich's ataxia. Specifically, the present invention provides a nucleic acid, cloning vector and transfer vector for the production of an adeno-associated virus (AAV) vector. The nucleic acid comprises (i) a nucleic acid sequence encoding frataxin, (ii) a phospho-glycerate-kinase (PGK) promoter, and (iii) a woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). The present invention also provides a pharmaceutical composition which comprises the AAV vector or nucleic acid. Also, the AAV vector, nucleic acid or pharmaceutical composition can be used as a medicament, specifically as a medicament for the treatment of Friedreich's ataxia.

The invention provides p38 MAPK inhibitors that compensate for a frataxin deficiency or mutation and methods of using the same (e.g., to treat Friedreich's ataxia).

The present disclosure relates to pharmaceutical compositions comprising a synthetic transcription elongation factor (SynTEF) and an epigenetic inhibitor (e.g., a histone deacetylase (HDAC) inhibitor). As detailed herein, the disclosed compositions and combinations can be used to target FGF14b in Friedreich's ataxia (FRDA / FA), SCA27b, and other GAA-repeat based diseases.

A recombinant adeno-associated virus (rAAV) comprising an AAV capsid and a vector genome comprising a frataxin gene is provided. Also provided is a composition containing an effective amount of rAAV to ameliorate symptoms of Freidreich's ataxia, including, e.g., reduction in progression towards neurocognitive decline and / or cardiomyopathy.

Provided herein are RNA editing oligonucleotides capable of effecting ADAR-mediated deamination of a target adenosine comprised in a target RNA, wherein the oligonucleotide comprises a sequence that is capable of hybridizing with a region in the target RNA comprising said target adenosine, and wherein the oligonucleotide comprises at least one conformationally restricted nucleotide (CRN) positioned at the 5' and / or at the 3' terminus of the oligonucleotide and / or internally. In particular, the target adenosine may be part of a therapeutic target codon in the MECP2 protein-coding RNA. Provided herein are RNA editing oligonucleotides capable of effecting ADAR-mediated deamination of a target adenosine in a target RNA molecule encoding a target protein, wherein the oligonucleotide comprises a sequence that is capable of hybridizing with a region in the target RNA molecule comprising said target adenosine, and wherein the target adenosine is part of a codon encoding a posttranslational modification site in the target protein. In particular, the target adenosine may be part of a ubiquitination site in the frataxin (FXN) protein. Provided herein are RNA editing oligonucleotides capable of effecting ADAR-mediated deamination of a target adenosine in a target RNA molecule encoding a target protein, wherein the oligonucleotide comprises a sequence that is capable of hybridizing with a region in the target RNA molecule comprising said target adenosine, and wherein the target adenosine is part of a start codon in the 5' untranslated region of the target RNA molecule. In particular, the target adenosine may be part of the start codon of an untranslated ORF (uORF) in the human Sodium-dependent phosphate transporter 2 protein (SLC20A2).

The present disclosure provides methods of increasing level of frataxin (FXN) in an FXN-decifient subject that comprise administering to the subject a TAT-FXN fusion protein once daily at a dose of about 25 mg or about 50 mg for at least 14 days. The present disclosure also provides methods of treating Friedreich's Ataxia (FRDA) in a subject that comprise administering to the subject a TAT-FXN fusion protein once daily at a dose of about 25 mg or about 50 mg for at least 14 days.

A recombinant adeno-associated virus (rAAV) comprising an AAV capsid and a vector genome comprising a frataxin gene is provided. Also provided is a composition containing an effective amount of rAAV to ameliorate symptoms of Freidreich's ataxia, including, e.g., reduction in progression towards neurocognitive decline and / or cardiomyopathy.

The present disclosure provides methods, compositions and kits for measuring activity of a frataxin (FXN) protein, e.g., an FXN fusion protein. The present invention also provides methods for identifying compounds capable of modulating activity of an FXN protein, e.g., an FXN fusion protein.

The present disclosure is based, at least in part, on providing a set of markers, also referred to herein as FXN-sensitive genomic markers (or FSGMs), the respective expression levels of which are positively or negatively correlated to frataxin (FXN) levels in a cell. Therefore, these FSGMs can be used to determine, evaluate, and / or monitor the effectiveness of FXN replacement therapy in a subject.

The present disclosure relates to compositions and methods for altering, e.g., enhancing the expression of ataxin (FXN), in vitro and / or in vivo, including but not limited to the development of engineered promoters. Such compositions include delivery by administration of adeno-associated virus (AAV) particles. The compositions and methods of the present disclosure are useful for treating a subject diagnosed with or suspected of having a Friedel's Ataxia or another neuromuscular or neurological condition that is caused by a lack of the amount and / or function of ataxin or that is associated with reduced expression or protein levels of ataxin.

Disclosed herein are antisense compounds and methods for decreasing Ataxin 2 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Ataxin 2 associated diseases, disorders, and conditions. Such Ataxin 2 associated diseases include spinocerebellar ataxia type 2 (SCA2), amyotropic sclerosis (ALS), and parkinsonism.

The present disclosure provides methods for determining the amount of FXN or FXN fusion protein in a sample, e.g., a tissue sample, by using mass spectrometry.

The disclosure relates to compositions and methods for, inter alia, altering, e.g., enhancing, the level of frataxin protein via delivery using an adeno-associated viral (AAV) capsid variant. The compositions and methods of the present disclosure are useful, inter alia, in the treatment of subjects who have, have been diagnosed with, or suspected of having a disorder associated with frataxin (FXN) deficiency, e.g., Friedreich's Ataxia.

The present disclosure provides methods, compositions, and kits for measuring the activity of Frataxin (FXN) protein, e.g., FXN fusion protein. The present invention also provides methods for identifying compounds capable of modulating the activity of FXN protein, e.g., FXN fusion protein.

A nucleic acid encoding human frataxin protein, a gene therapy vector including the nucleic acid, and genetically modified cells containing the nucleic acid or the vector are disclosed. The encoded human frataxin protein includes upstream cell secretion and cell penetration peptides. The genetically modified cells may be used in a method of treating Friedreich's Ataxia by transplanting a cell genetically modified by a gene therapy vector including the nucleic acid encoding human frataxin protein into a patient.

Described herein are compositions and methods for treating subjects with disorders associated with mutations in the FXN gene and / or that have reduced expression of frataxin protein, e.g., Friedreich ataxia (FRDA), using inhibitors of ferredoxin 2 (FDX2) that decreases FDX2 protein expression.

The present disclosure provides methods and compositions for improving cell viability, mitochondrial function and / or frataxin expression or treating Friedreich's ataxia (FRDA) comprising two or more of monomethyl fumarate (MMF) or a MMF prodrug such as dimethyl fumarate (DMF), nicotinamide (NAM), idebenone (IDB) and nitisinone (NTS).

The present disclosure is based, at least in part, on providing a set of markers, also referred to herein as FXN-sensitive genomic markers (or FSGMs), each expression level of which exhibits a positive or negative correlation with an ataxin (FXN) level in a cell. Thus, these FSGMs may be used to determine, assess, and / or monitor the efficacy of FXN replacement therapy in a subject.

The present disclosure provides methods of treating Friedreich's Ataxia (FRDA) in a subject that comprise administering to the subject a TAT-FXN fusion protein once daily at a dose of about 25 mg or a dose of about 50 mg. The present disclosure also provides methods of treating Friedreich's Ataxia (FRDA) in a pediatric subject that comprise administering to the subject a TAT-FXN fusion protein once daily at a dose of about 0.8 mg / kg, up to a maximum dose of about 50 mg. The present disclosure also provides methods of increasing the level of frataxin (FXN) in an FXN-decifient subject, e.g., pediatric subject.

The present invention provides methods and compositions of treating Friedreich's ataxia (FRDA) based on administering an mRNA encoding a frataxin protein.

Provided herein are expression cassettes for expressing a transgene in a cell, wherein the transgene encodes a disorder-related polypeptide. Also provided are methods to treat Friedreich's ataxia. Further provided herein are vectors (e.g., rAAV vectors), viral particles, pharmaceutical compositions and kits for expressing a disorder-related polypeptide in an individual in need thereof.