Compositions and methods for the treatment of leukodystrophy, particularly, H-ABC are disclosed.

The present disclosure relates to dual-cell model and Caenorhabditis elegans model systems for measuring neuron-to-neuron transmission of protein aggregates, and more particularly to transgenic cell and animal model systems expressing fusion proteins of N-terminus or C-terminus of fluorescent proteins with α-synuclein proteins, methods for measuring continuous cell-to-cell transmission of α-synuclein aggregates using the same, and methods for screening substances for preventing or treating neurodegenerative diseases.

Nervous system trauma and neurodegeneration including in optic neuropathies are treated by administration of an effective dose of a PDE4D3 displacing agent to promote neurite extension, neuroprotection and recovery. In some embodiments the neurons are optic neurons, including without limitation retinal ganglion cells (RGCs). A cAMP signaling compartment restricted by mAKAPα-anchored PDE4D3 directly regulates neuronal phenotype, and can be molecularly manipulated with therapeutic effect.

Provided are a patient-derived amyloid xenograft (PDAX) non-human animal model, uses and production methods thereof as well as methods comprising the model to determine/obtain anti-amyloid drugs suitable for the treatment of an amyloidosis or amyloid-related disease and methods and processes to characterize, validate, develop and/or quality control and manufacture such drugs.

Provided is a recombinant adeno-associated virus (rAAV) having an AAVhu68 capsid and a vector genome which comprises a nucleic acid sequence encoding a functional human arylsulfatase A (ARSA). Also provided are a production system useful for producing the rAAV, a pharmaceutical composition comprising the rAAV, and a method of treating a subject having metachromatic leukodystrophy, or ameliorating symptoms of metachromatic leukodystrophy, or delaying progression of metachromatic leukodystrophy via administering an effective amount of rAAV to a subject in need thereof.

An animal model for motor neuron dysfunction in disease, e.g., amyotrophic lateral sclerosis (ALS), comprising a genetically modified non-human animal that comprises a genetically modified DR6 allele and exhibits normal phenotypes at birth and for a few weeks or months after birth. However, as the non-human animal ages, it develops motor neuron dysfunction that presents as one or more ALS-like symptoms, which may progress rapidly after onset. Methods of identifying candidate agents that may be used to prevent, delay or treat ALS are also provided.

This invention relates to polynucleotides comprising optimized GALC open reading frame (ORF) sequences, vectors comprising the same, and methods of using the same for delivery of the ORF to a cell or a subject and to treat disorders associated with aberrant expression of a GALC gene or aberrant activity of a GALC gene product in the subject, such as Krabbe disease (i.e., globoid cell leukodystrophy (GLD)).

Disclosed herein are methods of treating HIBM in a subject comprising identifying subject in need thereof; and administering to the subject a compound, or a pharmaceutically acceptable salt, ester, amide, glycol, peptidyl, or prodrug thereof, wherein the compound is a compound that is biosynthesized in a wild type individual along a biochemical pathway between glucose and sialic acid, inclusive. Also disclosed herein are vectors comprising a nucleic acid sequence that encodes a polypeptide having at least 80% sequence identity to the sequence set forth in SEQ ID NO:2, recombinant cells comprising these vectors, and recombinant animals comprising the cells. In addition, methods of identifying a compound having therapeutic effect for HIBM are disclosed.

The present disclosure relates to a tyrosine hydroxylase (TH) variant lacking 60 to 120 amino acid residues at the N terminus, and a pharmaceutical composition comprising the TH variant lacking 60 to 120 amino acid residues at the N terminus and the aromatic L-amino acid decarboxylase (AADC). The present disclosure further relates to a nucleotide construct, a vector plasmid, a cell or a virus comprising the TH variant or the pharmaceutical composition, as well as use of the virus in the manufacture of a medicament for treating neurodegenerative diseases (e.g., Parkinson's Disease).

Provided herein is a differentiation agent that consist essentially of SOX9 for the production of oligodendrocyte progenitor cells (OPCs) from pluripotent stem cells (PSCs). Also provided herein are methods of producing the PSCs and methods of using the PSCs to produce OPCs and oligodendrocytes.