IP Library › Granted Patent US 12,358,959
Granted Patent B2
US 12,358,959 · App. 16/089,176 · Granted Jul 15, 2025

Compositions and methods for oligodendrocyte development

Inventor: Xianhua Piao (Boston, MA)
Assignee: Children's Medical Center Corporation
C07K14/47A61K35/30A61K38/45A61K47/543A61P25/00C07K14/723C12N9/1044C12Y203/02013A61K38/00
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Quick Facts
Patent No.
US 12,358,959
App. No.
16/089,176
Granted
Jul 15, 2025
Kind
B2
Abstract

The present invention provides compositions and methods for increasing myelination in the nervous system or a subject, including for the treatment of a disease or disorder characterized by a deficiency or loss of myelination (e.g., a demyelinating disease).

Claims (20)

1. A method of increasing myelination of a neuron and/or increasing oligodendrocyte or precursor thereof proliferation in a subject, the method comprising:

injecting an effective amount of a vector into the subject thereby contacting an oligodendrocyte or precursor thereof comprising GPR56 in the subject with the vector comprising a nucleotide sequence encoding:

an amino acid sequence TYFAVLMVS (SEQ ID NO: 1),

wherein the SEQ ID NO:1 binds GPR56.

2. The method of claim 1 , wherein the subject has bilateral frontoparietal polymicrogyria (BFPP).

3. The method of claim 2 , wherein the subject has a GPR56 allele comprising a loss-of-function mutation.

4. A method of increasing myelination and/or oligodendrocyte or precursor thereof proliferation in a subject, the method comprising:

injecting an effective amount of a vector into the subject thereby contacting an oligodendrocyte or precursor thereof comprising GPR56 in the subject with the vector comprising a nucleotide sequence encoding:

an amino acid sequence TYFAVLMVSSVEVDAVHKHYLS (SEQ ID NO: 2),

wherein SEQ ID NO:2 binds GPR56.

5. The method of claim 4 , wherein the subject suffers from a demyelinating disease, said demyelinating disease is selected from the group consisting of: multiple sclerosis, periventricular leukodystrophy, periventricular leukomalacia, optic neuritis, neuromyelitis optica, acute disseminated encephalomyelitis, idiopathic inflammatory demyelinating disease, central pontine myelolysis, and progressive multifocal leukoencephalopathy.

6. The method of claim 1 , wherein the amino acid sequence TYFAVLMVS (SEQ ID NO: 1) is a tethered ligand.

7. The method of claim 1 , wherein the amino acid sequence TYFAVLMVS (SEQ ID NO: 1) is covalently linked to a lipid or transmembrane domain.

8. The method of claim 1 , wherein the N-terminus or C-terminus of the amino acid sequence TYFAVLMVS (SEQ ID NO: 1) is covalently linked to a lipid or transmembrane domain.

9. The method of claim 4 , wherein the amino acid sequence TYFAVLMVSSVEVDAVHKHYLS (SEQ ID NO: 2) is a tethered ligand.

10. The method of claim 1 , wherein the subject suffers from a demyelinating disease, said demyelinating disease is selected from the group consisting of: multiple sclerosis, periventricular leukodystrophy, periventricular leukomalacia, optic neuritis, neuromyelitis optica, acute disseminated encephalomyelitis, idiopathic inflammatory demyelinating disease, central pontine myelolysis, and progressive multifocal leukoencephalopathy.

11. The method of claim 4 , wherein the subject has bilateral frontoparietal polymicrogyria (BFPP).

12. The method of claim 11 , wherein the subject has a GPR56 allele comprising a loss-of-function mutation.

13. The method of claim 4 , wherein the amino acid sequence TYFAVLMVSSVEVDAVHKHYLS (SEQ ID NO: 2) is covalently linked to a lipid or transmembrane domain.

14. The method of claim 4 , wherein the N-terminus or C-terminus of the amino acid sequence TYFAVLMVSSVEVDAVHKHYLS (SEQ ID NO: 2) is covalently linked to a lipid or transmembrane domain.

Assignments (2)
CONFIRMATORY LICENSE Recorded Jul 22, 2019
From: BOSTON CHILDREN'S HOSPITAL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 049823/0683 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 1, 2018
From: PIAO, XIANHUA
To: CHILDREN'S MEDICAL CENTER CORPORATION
Reel/Frame 047016/0967 →
Continuity (2)
Provisional Application 62316491 · Mar 31, 2016
Related Publication 20190119338A1 · Apr 25, 2019
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