Methods of treating neurodegenerative disorders

A method of preventing a neurodegenerative disorder comprising administering to the subject a therapeutically effective amount of a vector comprising a nucleic acid that encodes trehalose-6-phosphate synthase (OtsA), a nucleic acid that encodes trehalose 6-phosphate phosphatase (OtsB), a nucleic acid that encodes OtsA and OtsB, or a nucleic acid that encodes a trehalose biosynthesis fusion polypeptide.

A method of treating a subject having a neurodegenerative disorder comprising administering to the subject a therapeutically effective amount of trehalose and a therapeutically effective amount of a vector comprising a nucleic acid that encodes trehalose-6-phosphate synthase (OtsA), a nucleic acid that encodes trehalose 6-phosphate phosphatase (OtsB), a nucleic acid that encodes OtsA and OtsB, or nucleic acid that encodes a trehalose biosynthesis fusion polypeptide.

A method of treating a subject in need thereof, the method comprising

• (a) identifying the subject as having a neurodegenerative disorder;
• and
• (b) administering to the subject a therapeutically effective amount of a vector comprising a nucleic acid that encodes trehalose-6-phosphate synthase (OtsA), a nucleic acid that encodes trehalose 6-phosphate phosphatase (OtsB), a nucleic acid that encodes OtsA and OtsB, or a nucleic acid that encodes a trehalose biosynthesis fusion polypeptide.

The method of any of the preceding claims, wherein the neurodegenerative disorder is associated with the formation of protein plaques.

The method of any of the preceding claims, wherein the neurodegenerative disorder is selected from the group consisting of Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), ataxia (e.g., Friedreich's ataxia), progressive supranuclear palsy (PSLP), spinocerebellar ataxia (SCA) (e.g., SCA3), and amyloidosis.

The method of any one of the preceding claims, wherein the vector comprises a nucleic acid that encodes OtsA and OtsB.

The method of any one of the preceding claims, wherein the vector further comprises an enhancer.

The method of any of the preceding claims, wherein the vector is an adeno-associated viral (AAV) vector.

The method of any one of the preceding claims, wherein the vector comprises a nucleic acid that encodes a trehalose biosynthesis fusion polypeptide.

The method of any one of the preceding claims, wherein the nucleic acid encoding the trehalose biosynthesis fusion polypeptide comprises a nucleic acid encoding OtsA, or a functional fragment thereof and a nucleic acid encoding OtsB, or a functional fragment thereof.

The method of any of the preceding claims, wherein the nucleic acid that encodes trehalose-6-phosphate synthase (OtsA), the nucleic acid that encodes trehalose 6-phosphate phosphatase (OtsB), the nucleic acid that encodes OtsA and OtsB, or the nucleic acid encoding a trehalose biosynthesis fusion polypeptide is operably linked to a promoter.

The method of any of the preceding claims, wherein the administering is intrathecal, intraparenchymal, intracisterna (ICM), or intracerebroventricular injection (ICV).

The method of any one of the preceding claims, wherein the subject is a mammal.

A method of treating a subject having a disorder associated with excessive inflammation comprising administering to the subject a therapeutically effective amount of a vector comprising a nucleic acid that encodes trehalose-6-phosphate synthase (OtsA), a nucleic acid that encodes trehalose 6-phosphate phosphatase (OtsB), a nucleic acid that encodes OtsA and OtsB, or a nucleic acid encoding a trehalose biosynthesis fusion polypeptide.

A method of preventing symptoms of a subject having a disorder associated with excessive inflammation comprising administering to the subject a therapeutically effective amount of a vector comprising a nucleic acid that encodes trehalose-6-phosphate synthase (OtsA), a nucleic acid that encodes trehalose 6-phosphate phosphatase (OtsB), a nucleic acid that encodes OtsA and OtsB, or a nucleic acid encoding a trehalose biosynthesis fusion polypeptide.

A vector comprising a nucleic acid that encodes trehalose-6-phosphate synthase (OtsA), a nucleic acid that encodes trehalose 6-phosphate phosphatase (OtsB), a nucleic acid that encodes OtsA and OtsB, or a nucleic acid that encodes a trehalose biosynthesis fusion polypeptide.

The vector of any one of the preceding claims, wherein the nucleic acid that encodes OtsA is SEQ ID NO:

• 1.

The vector of any one of the preceding claims, wherein the OtsA comprises SEQ ID NO:

• 2.

The vector of any one of the preceding claims, wherein the nucleic acid that encodes OtsB is SEQ ID NO:

• 3.

The vector of any one of the preceding claims, wherein the OtsB comprises SEQ ID NO:

• 4.

The vector of any one of the preceding claims, wherein the nucleic acid that encodes OtsA and OtsB, or the nucleic acid encoding a trehalose biosynthesis fusion polypeptide comprises SEQ ID NO:

• 5.

The vector of any one of the preceding claims, wherein the trehalose biosynthesis fusion polypeptide comprises SEQ ID NO:

• 6.

The vector of any one of the preceding claims, wherein the nucleic acid that encodes P2A is SEQ ID NO:

• 7.

The vector of any one of the preceding claims, wherein the P2A comprises SEQ ID NO:

• 8.

The vector of any one of the preceding claims, wherein the nucleic acid that encodes T2A is SEQ ID NO:

• 9.

The vector of any one of the preceding claims, wherein the T2A comprises SEQ ID NO:

• 10.

The method of any one of the preceding claims, wherein the nucleic acid that encodes OtsA is SEQ ID NO:

• 1.

The method of any one of the preceding claims, wherein the OtsA comprises SEQ ID NO:

• 2.

The method of any one of the preceding claims, wherein the nucleic acid that encodes OtsB is SEQ ID NO:

• 3.

The method of any one of the preceding claims, wherein the OtsB comprises SEQ ID NO:

• 4.

The method of any one of the preceding claims, wherein the nucleic acid that encodes OtsA and OtsB, or the nucleic acid encoding a trehalose biosynthesis fusion polypeptide comprises SEQ ID NO:

• 5.

The method of any one of the preceding claims, wherein the trehalose biosynthesis fusion polypeptide comprises SEQ ID NO:

• 6.

The method of any one of the preceding claims, wherein the nucleic acid that encodes P2A is SEQ ID NO:

• 7.

The method of any one of the preceding claims, wherein the P2A comprises SEQ ID NO:

• 8.

The method of any one of the preceding claims, wherein the nucleic acid that encodes T2A is SEQ ID NO:

• 9.

The method of any one of the preceding claims, wherein the T2A comprises SEQ ID NO:

• 10.