METHOD FOR TREATING NEUROLOGICAL DISORDERS

• US 20110071088A1
• Filed: 05/28/2010
• Published: 03/24/2011
• Est. Priority Date: 12/16/2003
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Benowitz, Larry I.
• Granted Patent: US 8,912,144 B2
• Time in Patent Office: Days
• US Class Current: 514/17.8
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: 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
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2750/14143 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2750/14145 Special targeting system for viral vectors

Abstract

The present invention is based on the discovery that suppressing the activity of the Nogo receptor (NgR) alone does not result in extensive axon regeneration unless the intrinsic growth program of neurons is also activated. Accordingly, the present invention is directed to methods of stimulating axon regeneration using a combination therapy wherein agents that inhibit NgR activity or downstream pathways activated by inhibitory signals are combined with agents that activate the growth pathway of neurons (e.g. polypeptide growth factors, activators of macrophages, purine nucleosides, or hexoses).

Claims

1. A method for stimulating axonal outgrowth of central nervous system (CNS) neurons comprising contacting the CNS neurons with an effective amount of NEP1-40 and insoine, to thereby stimulate axonal outgrowth.

2. The method of claim 1, wherein said CNS neurons are mammalian.

3. The method of claim 1, further comprising contacting the CNS neurons with a cAMP modulator that increases the concentration of intracellular cAMP.

4. The method of claim 3, wherein the cAMP modulator is selected from the group consisting of:

cAMP analogues, activators of G protein coupled receptors that activate cAMP, adenylate cyclase activators, calcium ionophores, and phosphodiesterase inhibitors.

5. A method for treating a neurological disorder in a patient in need thereof comprising administering an effective amount of NEP1-40 and insoine to the patient, to thereby treat the neurological disorder.

6. The method of claim 5, wherein the neurological disorder is selected from the group consisting of traumatic brain injury, stroke, cerebral aneurism, spinal cord injury, 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, ophthalmoplegia, and retina or optic nerve damage.

7. The method of claim 5, wherein the NEP1-40 and insoine are administered following an injury to the CNS, to thereby re-establish neural connectivity and/or function after the CNS injury,

8. The method of claim 5, wherein the NEP1-40 and insoine are administered by a route selected from the group consisting of topical, pulmonary, internal topical, interdermal, intravenous, subcutaneous, intranasal, epidermal, ophthalmic, oral, intraventricular, and intrathecal.

9. A pharmaceutical composition comprising NEP1-40 and inosine.

10. The pharmaceutical composition of claim 9, wherein the composition is formulated for a route of administration selected from the group consisting of topical, pulmonary, internal topical, interdermal, intravenous, subcutaneous, intranasal, epidermal, ophthalmic, oral, intraventricular, and intrathecal.