# US 9,750,753 B1 · Method of treating diseases associated with LRRK2 mutation using hexachlorophene

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- Number: US 9,750,753 B1
- Document ID: US9750753B1
- Status: Granted
- Kind: B1
- Application number: 14/742,116
- Filed: 2015-06-17
- Granted: 2017-09-05
- Earliest claimed: 2014-06-17
- Assignees: University of South Florida
- Applicants: Umesh K. Jinwal; Malathi Narayan
- Inventors: Umesh K. Jinwal; Malathi Narayan
- Web page: https://patentgrep.com/patent/US9750753B1

## CPC

- A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048})
- A61K 31/05: Phenols {(cannabinoids A61K31/658)}
- A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60)
- 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)

## Abstract

A method of treating a disease associated with mutation of LRRK2 protein is presented herein. It was found that administering hexachlorophene to cells expressing endogenous LRRK2 or overexpressing wild-type or mutant LRRK2 reduced the total LRRK2 level in the cells.

## Claims

### Claim 1

A method of treating a disease characterized by mutation of LRRK2 protein in a patient in need thereof comprising administering a therapeutically effective amount of hexachlorophene, wherein the hexachlorophene is administered concomitantly with a drug selected from the group consisting of withaferin A and celastrol.

### Claim 2 (depends on 1)

The method of claim 1, wherein the disease is Parkinson's disease.

### Claim 3 (depends on 1)

The method of claim 1, wherein the disease is an autoimmune disease selected from the group consisting of Crohn's disease, leprosy, rheumatoid arthritis and psoriasis.

### Claim 4 (depends on 1)

The method of claim 1, further comprising encapsulating the hexachlorophene in a vesicle prior to administration to the patient.

### Claim 5 (depends on 4)

The method of claim 4, wherein the vesicle is selected from the group consisting of liposomes, niosomes, micelles, multilamellar vesicles, unilamellar vesicles, and polymersomes.

### Claim 6 (depends on 1)

The method of claim 1, further comprising administering a pre-administration agent at a time period prior to administration of the hexachlorophene.

### Claim 7 (depends on 6)

The method of claim 6, wherein the pre-administration agent is an antioxidant.

### Claim 8 (depends on 7)

The method of claim 7, wherein the antioxidant is selected from the group consisting of butylated hydroxytoluene (BHT), ethoxyquin and L-carnitine.

### Claim 9 (depends on 6)

The method of claim 6, wherein the pre-administration agent is selected from the group consisting of butylated hydroxytoluene (BHT), ethoxyquin, L-carnitine, phenobarbital, or SKF-525A.

### Claim 10 (depends on 6)

The method of claim 6, wherein the pre-administration agent is administered to the patient at least once per day for at least one day prior to administration of the hexachlorophene.

### Claim 11

A method of reducing LRRK2 protein expression levels in a cell comprising contacting the cell with a therapeutically effective amount of hexachlorophene, further comprising administering a Hsp90 inhibitor concomitantly with the hexachlorophene, wherein the Hsp90 inhibitor is selected from withaferin A (WA) and celastrol.

### Claim 12

A method of inhibiting LRRK2 activity in a cell comprising contacting the cell with a therapeutically effective amount of hexachlorophene, further comprising administering a Hsp90 inhibitor concomitantly with the hexachlorophene, wherein the Hsp90 inhibitor is selected from withaferin A (WA) and celastrol.