# US 6,294,585 B1 · Treatment of neurodegenerative diseases

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- Number: US 6,294,585 B1
- Document ID: US6294585B1
- Status: Granted
- Kind: B1
- Application number: 08/933,145
- Filed: 1997-09-18
- Granted: 2001-09-25
- Earliest claimed: 1996-09-18
- Assignees: Applied Genetics Incorporated Dermatics
- Inventors: David A. Brown
- Web page: https://patentgrep.com/patent/US6294585B1

## CPC

- A61K 31/047: having two or more hydroxy groups, e.g. sorbitol
- A61K 31/045: Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61P 17/00: Drugs for dermatological disorders
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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

## Abstract

Disclosed are methods for increasing the differentiation of mammalian neuronal cells for purposes of treating neurodegenerative diseases or nerve damage by administration of various compounds including alcohols, diols and/or triols and their analogues.

## Claims

### Claim 1

A method for increasing the differentiation of mammalian neuronal cells to a statistically significant level above background, which comprises administering to mammalian cells in need of such increase a pharmaceutical composition comprising an effective amount of one or more diols having the following structure:
wherein
each R is independently selected from hydrogen; halogen; a group containing from one atom to twenty atoms, one of which is carbon, nitrogen, oxygen, or sulfur; hydroxyl; hydroxymethyl; —(CH2)nOH; —(CH2)nOR′; —(CH2)n—CH(OH)—CHOH; —(CH2)n—CH(OH)—CH(OH)R′;—(CH2)n—CH(OH)—(CH2)n—CH2(OH); —(CH2)n—CH(OH)—(CH2)n—CH(OH)R′; or —CH2OR′; wherein each n is independently an integer from 0-25;
each R′ is independently selected from hydrogen or an acyl or amino acyl group containing from one atom to twenty atoms, at least one of which is carbon, nitrogen, oxygen, or sulfur;
or pharmaceutically acceptable salts thereof, and
a pharmaceutically suitable carrier.

### Claim 2 (depends on 1)

The method of claim 1, wherein the diol is selected from the group consisting of 5-norbornene-2,2-dimethanol, norbornane-2,2-dimethanol, 2,3-norbornanediol (exo or endo or cis or trans), 2,3-cis-exo-norbornanediol, and 2-endo-hexadecylamino-5-norbornene-2,3-exo-dimethanol.

### Claim 3 (depends on 2)

The method of claim 2, wherein the diol is selected from 5-norbornene-2,2-dimethanol; norbornane-2,2-dimethanol; and 2,3-cis-exo-norbornanediol.

### Claim 4

A pharmaceutical composition for increasing the differentiation of mammalian neuronal cells to a statistically significant level above background, which comprises:
a) an effective amount of one or more diols having the following structure:
wherein
each R is independently selected from hydrogen; halogen; a group containing from one atom to twenty atoms, one of which is carbon, nitrogen, oxygen, or sulfur; hydroxyl; hydroxymethyl; —(CH2)nOH, —(CH2)nOR′; —(CH2)n—CH(OH)—CHOH; —(CH2)n—CH(OH)—CH(OH)R′; —(CH2)n—CH(OH)—(CH2)n—CH2(OH); —(CH2)n—CH(OH)—(CH2)n—CH(OH)R′; or —CH2OR′; wherein each n is independently an integer from 0-25;
each R′ is independently selected from hydrogen or an acyl or amino acyl group containing from one atom to twenty atoms, at least one of which is carbon, nitrogen, oxygen, or sulfur;
or pharmaceutically acceptable salts thereof; and
b) a pharmaceutically suitable carrier.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the diol is selected from the group consisting of 5-norbornene-2,2-dimethanol, norbornane-2,2-dimethanol, 2,3-norbornanediol (exo or endo or cis or trans), 2,3-cis-exo-norbornanediol, and 2-endo-hexadecylamino-5-norbornene-2,3-exo-dimethanol.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the diol is selected from 5-norbornene-2,2-dimethanol; norbornane-2,2-dimethanol; and 2,3-cis-exo-norbornanediol.

### Claim 7 (depends on 1)

The method of claim 1, wherein the differentiation reverses neuronal damage.

### Claim 8 (depends on 1)

The method of claim 1, wherein the differentiation alleviates a neurodegenerative disease.

### Claim 9 (depends on 8)

The method of claim 8, wherein the disease is selected from the group consisting of Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, diffuse cerebral cortical atrophy, Lewy-body dementia, Pick disease, mesolimbocortical dementia, thalamic degeneration, Huntington chorea, cortical-striatal-spinal degeneration, cortical-basal ganglionic degeneration, cerebrocerebellar degeneration, familial dementia with spastic paraparesis, polyglucosan body disease, Shy-Drager syndrome, olivopontocerebellar atrophy, progressive supranuclear palsy, dystonia musculorum deformans, Hallervorden-Spatz disease, Meige syndrome, familial tremors, Gilles de la Tourette syndrome, acanthocytic chorea, Friedreich ataxia, Holmes familial cortical cerebellar atrophy, Gerstmann-Straussler-Scheinker disease, progressive spinal muscular atrophy, progressive balbar palsy, primary lateral sclerosis, hereditary muscular atrophy, spastic paraplegia, peroneal muscular atrophy, hypertrophic interstitial polyneuropathy, heredopathia atactica polyneuritiformis, optic neuropathy, and ophthalmoplegia.

### Claim 10 (depends on 1)

The method of claim 1, wherein the differentiation alleviates a cancerous, tumorous or proliferative disorder.

### Claim 11 (depends on 1)

The method of claim 1 wherein the mammalian cells are a mammal.

### Claim 12 (depends on 4)

The composition of claim 4 wherein the mammalian cells are a mammal.

### Claim 13 (depends on 1)

The method of claim 1 wherein the increase in differentiation of neuronal cells is sufficient to form neurite outgrowth on PC12 cells in at least about 25% of the cells.

### Claim 14 (depends on 4)

The composition of claim 4 wherein the increase in differentiation of neuronal cells is sufficient to form neurite outgrowth on PC12 cells in at least about 25% of the cells.

### Claim 15 (depends on 4)

The composition of claim 4 wherein the differentiation reverses neuronal damage.

### Claim 16 (depends on 4)

The composition of claim 4 wherein the differentiation alleviates a neurodegenerative disease.

### Claim 17 (depends on 16)

The composition of claim 16 wherein the disease is selected from the group consisting of Parkinson's disease, amyotrophic lateral schlerosis, Alzheimer's disease, diffuse ceregral cortical atrophy, Lewy-body dimentia, Pick disease, mesolimbocortical dementia, thalamic degeneration, Huntington chorea, cortical-striatal-spinal degeneration, cortical-basal ganglionic degeneration, cerebrocerebellar degeneration, familial dementia with spastic paraparesis, polyglucosan body disease, Shy-Drager syndrome, olivopontocerebellar atrophy, progressive supranuclear palsy, dystonia musculorum defoimans, Hallervorden-Spatz disease, Meige syndrome, familial tremors, Gilles de la Tourette syndrome, acanthocytic chorea, Friedreich ataxia, Holmes familial cortical cerebellar atrophy, Gerstmann-Straussler-Scheinker disease, progressive spinal muscular atrophy, progressive balbar palsy, primary lateral sclerosis, hereditary muscular atrophy, spastic paraplegia, peroneal muscular atrophy, hyupertrophic interstitial polyneuropathy, heredopathia atactica polyneuritiformis, optic neuropathy and ophthalmoplegia.

### Claim 18 (depends on 4)

The composition of claim 4 wherein the differentiation alleviates a cancerous, tumorous or proliferative disorder.

### Claim 19 (depends on 1)

The method of claim 1 wherein the composition is in a unitary dose.

### Claim 20 (depends on 4)

The composition of claim 4 in a unitary dose.