IP Library › Granted Patent US 12,514,911
Granted Patent B2
US 12,514,911 · App. 17/835,668 · Granted Jan 6, 2026

Metabolic therapy for oxidative stress in the brain through targeted neuronal catabolism of N-acetyl-aspartic acid

Inventors: Paola Leone (Cherry Hill, NJ); Jeremy Francis (Cherry Hill, NJ)
Assignee: ROWAN UNIVERSITY
A61K38/50A61K35/30A61K38/52C12N15/86C12Y305/01015C12N2750/14141
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Quick Facts
Patent No.
US 12,514,911
App. No.
17/835,668
Granted
Jan 6, 2026
Kind
B2
Abstract

The present invention provides a novel method of treatment for treating brain disorders that manifest oxidative stress by providing targeted populations of neurons with the ability to catabolize the acetylated amino acid derivative, N-acetylaspatic acid (NAA) and further supply extraphysiological levels of ATP to neurons via the targeted expression of the NAA catabolic enzyme aspartoacylase (ASPA) in neurons and astrocytes.

Claims (22)

1 . A method of reducing oxidative stress in a subject suffering from or at risk for Huntington's disease, the method comprising:

(a) identifying a subject suffering from or at risk for Huntington's disease; and

(b) administering to the subject an effective amount of a formulation comprising an isolated nucleic acid comprising a nucleotide sequence that encodes aspartoacylase (ASPA) under conditions whereby the nucleic acid is expressed in a host cell of the subject and whereby expression of ASPA leads to enhanced catabolism of NAA, increased concentration of AcCoA, and reduced oxidative stress.

2 . The method of claim 1 , wherein the host cell is a nerve cell selected from the group consisting of oligodendrocytes, neurons, astrocytes, and any combination thereof.

3 . The method of claim 1 , wherein the host cell is a central nervous system cell.

4 . The method of claim 3 , wherein the central nervous system cell is a neuron.

5 . The method of claim 1 , further comprising administration of a secondary therapeutic product to treat a condition arising from or related to Huntington's disease selected from the group consisting of an antibody, a cultured cell, an active substance and a diagnostic agent.

6 . The method of claim 1 , wherein the nucleic acid is in a vector and operatively linked to a promoter.

7 . The method of claim 6 , wherein the vector is an adeno-associated virus (AAV) vector comprising a regulatory element.

8 . The method of claim 7 , wherein the AAV vector is an AAV2 vector.

9 . The method of claim 1 , wherein the nucleotide sequence that encodes ASPA is set forth in SEQ ID NO: 1.

10 . The method of claim 1 , wherein the AAV2 vector further comprises bovine growth hormone polyA, the promoter is neuron specific enolase, and the regulatory element is woodchuck hepatitis virus post-translational regulatory element.

11 . A method for improving the disease phenotype of a subject at risk for or suffering from Huntington's disease, the method comprising administering to the subject an effective amount of a formulation comprising an isolated nucleic acid comprising a nucleotide sequence that encodes ASPA under conditions whereby the nucleic acid is expressed in a host cell of the subject and whereby expression of ASPA leads to enhanced catabolism of NAA, increased concentration of AcCoA, and reduced oxidative stress, wherein the formulation is administered to a tissue afflicted by the disease.

12 . The method of claim 11 , wherein the tissue is selected from the group consisting of cerebral cortex, intracranial white matter, basal ganglia, thalamus, hypothalamus, brain stem, and cerebellum.

13 . The method of claim 11 , wherein the nucleotide sequence that encodes ASPA is set forth in SEQ ID NO: 1.

14 . The method of claim 13 , further comprising administration of a secondary therapeutic product to treat a condition arising from or related to Huntington's disease selected from the group consisting of an antibody, a cultured cell, an active substance and a diagnostic agent.

15 . The method of claim 11 , wherein the host cell is a nerve cell selected from the group consisting of oligodendrocytes, neurons, astrocytes, and any combination thereof.

16 . The method of claim 11 , wherein the host cell is a central nervous system cell.

17 . The method of claim 16 , wherein the central nervous system cell is a neuron.

18 . The method of claim 11 , wherein the nucleic acid is in a vector and operatively linked to a promoter.

19 . The method of claim 18 , wherein the vector is an adeno-associated virus (AAV) vector comprising a regulatory element.

20 . The method of claim 19 , wherein the AAV vector is an AAV2 vector.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 8, 2025
From: UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY
To: ROWAN UNIVERSITY
Reel/Frame 071974/0732 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 8, 2025
From: LEONE, PAOLA; FRANCIS, JEREMY
To: UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY
Reel/Frame 071974/0780 →
Continuity (5)
Division 16508870 · Jul 11, 2019
Continuation 15644313 · Jul 7, 2017
Continuation 13906171 · May 30, 2013
Provisional Application 61653087 · May 30, 2012
Related Publication 20220305097A1 · Sep 29, 2022
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