# US 11,998,602 B2 · Methods for promoting myelination and for treating demyelinating diseases

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- Number: US 11,998,602 B2
- Document ID: US11998602B2
- Status: Granted
- Kind: B2
- Application number: 16/978,558
- Filed: 2018-11-13
- Published: 2021-01-28
- Granted: 2024-06-04
- Earliest claimed: 2018-03-08
- Assignees: The Scripps Research Institute
- Applicants: The Scripps Research Institute
- Inventors: Luke Lairson; Brittney Beyer; Mingliang Fang; Gary Siuzdak
- Web page: https://patentgrep.com/patent/US11998602B2

## CPC

- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 31/185: Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327)
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 31/4174: Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
- A61K 31/46: 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61P 25/00: Drugs for disorders of the nervous system
- C07C 303/02: of sulfonic acids or halides thereof
- C07K 16/286: {against neuromediator receptors, e.g. serotonin receptor, dopamine receptor}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

This invention provides novel methods for treating or ameliorating symptoms of demyelinating diseases such as multiple sclerosis. The methods involve administering to subjects in need of treatment a pharmaceutical composition that contains a therapeutically effective amount of taurine and also a compound that induces oligodendrocyte precursor cell (OPC) differentiation (e.g., T3, benztropine, clemastine or miconazole). Some of the methods additionally involve administration to the subject a known agent for treating demyelinating diseases (e.g., SIP receptor agonists) or a known disease modifying drug. The invention also provides methods for increasing myelination and methods for promoting OPC differentiation into oligodendrocytes. These methods entail contacting a population of OPCs with a combination of taurine and a known OPC differentiation-inducing agent such as T3, clemastine, benztropine or miconazole.

## Claims

### Claim 1

A method for treating or ameliorating one or more symptoms of a demyelinating disease in a subject, comprising administering to the subject (a) a pharmaceutical composition comprising a therapeutically effective amount of taurine or a taurine-like compound and (b) an agent that induces oligodendrocyte precursor cell (OPC) differentiation, thereby treating or ameliorating the symptoms of the demyelinating disease in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the taurine or taurine-like compound is administered to the subject simultaneously with, prior to, or subsequent to administration of the agent that induces OPC differentiation.

### Claim 3 (depends on 1)

The method of claim 1, wherein the taurine-like compound is an agent that can directly or indirectly upregulate the serine level in an OPC, pre-myelinating oligodendrocyte, or oligodendrocyte, thereby enhancing glycosphingolipid biosynthesis in the OPC, pre-myelinating oligodendrocyte, or oligodendrocyte.

### Claim 4 (depends on 1)

The method of claim 1, wherein the taurine-like compound is a taurine precursor, a taurine metabolite, a taurine derivative, a taurine analog, or a substance required for taurine biosynthesis.

### Claim 5 (depends on 1)

The method of claim 1, wherein the demyelinating disease is multiple sclerosis (MS).

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject is a human.

### Claim 7 (depends on 1)

The method of claim 1, wherein the agent that induces OPC differentiation is a muscarinic receptor antagonist, a dopamine receptor antagonist, a histamine receptor antagonist, a beta adrenergic receptor modulator, or an opioid receptor modulator.

### Claim 8 (depends on 1)

The method of claim 1, wherein the agent that induces OPC differentiation is benztropine, clemastine, miconazole, triiodothyronine (T3), or clobetasol .

### Claim 9 (depends on 1)

The method of claim 1, further comprising administering to the subject a known agent for treating a demyelinating disease or a disease modifying drug.

### Claim 10 (depends on 9)

The method of claim 9, wherein the known agent for treating a demyelinating disease is an S1P receptor agonist.

### Claim 11 (depends on 10)

The method of claim 10, wherein the S1P receptor agonist is FTY720, MT1303, ACT-128800, BAF312, GSK2018682, CYM-5442, ONO-4641, AUY954, RG3477, SEW-2871, CS-0777, Syl930, AAL-R, RPC1063, RP-001, KRP-203, or CYM-5442.

### Claim 12 (depends on 9)

The method of claim 9, wherein the known agent for treating a demyelinating disease or disease modifying drug is administered to the subject prior to, simultaneously with, or subsequent to administration of the pharmaceutical composition comprising a therapeutically effective amount of taurine or a taurine-like compoundi and/or the agent that induces OPC differentiation.

### Claim 13

A method for increasing myelination in a subject, comprising administering to the subject (a) a pharmaceutical composition comprising a therapeutically effective amount of taurine or a taurine-like compound, and (b) an agent that induces OPC differentiation.

### Claim 14 (depends on 13)

The method of claim 13, wherein the subject is a human.

### Claim 15 (depends on 13)

The method of claim 13, wherein the pharmaceutical composition is administered to the subject simultaneously with, prior to, or subsequent to administration of the agent that induces OPC differentiation.

### Claim 16 (depends on 13)

The method of claim 13, wherein the subject is afflicted with or is at risk of developing a demyelinating disease.

### Claim 17 (depends on 16)

The method of claim 16, wherein the demyelinating disease is multiple sclerosis (MS).

### Claim 18

A pharmaceutical composition, comprising (a) a therapeutically effective amount of taurine or a taurine-like compound and (b) one or more agents that induce OPC differentiation or treat a demyelinating disease.

### Claim 19 (depends on 18)

The pharmaceutical composition of claim 18, further comprising a pharmaceutically acceptable carrier.

### Claim 20 (depends on 18)

The pharmaceutical composition of claim 18, wherein the one or more agents that induce OPC differentiation or treat a demyelinating disease is benztropine, clemastine, miconazole, triiodothyronine (T3), clobetasol, or a S1P receptor agonist.