Claims
- 1. A method for promoting survival and/or functional perfomance of neuronal cells susceptible to exotoxicity, comprising contacting the cells with an amount of a lipophilic modified hedgehog polypeptide effective to reduce exotoxin-mediated degradation of the cells.
- 2. A method for promoting survival of substantia nigra neuronal cells comprising contacting the cells with a trophic amount of a lipophilic modified hedgehog polypeptide.
- 3. A method for promoting survival of dopaminergic cells comprising contacting the cells with a trophic amount of a lipophilic modified hedgehog polypeptide.
- 4. A method for promoting survival of GABAergic cells comprising contacting the cells with a trophic amount of a lipophilic modified hedgehog polypeptide or a lipophilic modified hedgehog polypeptide.
- 5. A method for the treating a disorder characterized by loss of dopaminergic and/or GABAergic neurons which comprises administering to a patient in need thereof a therapeutically effective amount of lipophilic modified hedgehog polypeptide.
- 6. A method for the treating or preventing Parkinson's disease comprising administering to a patient in need thereof a therapeutically effective amount of lipophilic modified hedgehog polypeptide.
- 7. A method for the treating or preventing Huntington's disease comprising administering to a patient in need thereof a therapeutically effective amount of lipophilic modified hedgehog polypeptide.
- 8. A method for treatment or prophylaxis of a disorder selected from the group consisting of
domoic acid poisoning; spinal cord trauma; hypoglycemia; mechanical trauma to the nervous system; senile dementia; Korsakoff's disease; schizophrenia; AIDS dementia, multi-infarct dementia; mood disorders; depression; chemical toxicity; neuronal damage associated with uncontrolled seizures, such as epileptic seizures; neuronal injury associated with HIV and AIDS; neurodegeneration associated with Down's syndrome; neuropathic pain syndrome; olivopontocerebral atrophy; amyotrophic lateral sclerosis; mitochondrial abnormalities; Alzheimer's disease; hepatic encephalopathy; Tourette's syndrome; schizophrenia; and drug addiction, comprising administering to a patient in need thereof a therapeutically effective amount of lipophilic modified hedgehog polypeptide.
- 9. The method of any of claims 1-8, wherein the hedgehog polypeptide is modified with one or more serol moieties.
- 10. The method of claim 9, wherein the sterol moiety is cholesterol.
- 11. The method of any of claims 1-8, wherein the hedgehog polypeptide is modified with one or more fatty acid moieties.
- 12. The method of claim 11, wherein each fatty acid moiety is independently selected from the group consisting of myristoyl, palmitoyl, stearoyl, and arachidoyl.
- 13. The method of any of claims 1-8, wherein the hedgehog polypeptide is modified with one or more aromatic hydrocarbons.
- 14. The method of claim 13, wherein each aromatic hydrocarbon is ondependently selected from the group consisting of benzene, perylene, phenanthrene, anthracene, naphthalene, pyrene, chrysene, and naphthacene.
- 15. The method of any of claims 1-8, wherein the hedgehog polypeptide is odified one or more times with a C7-C30 alkyl or cycloalkyl.
- 16. The method of any of claims 5-8, wherein patient is being treated prophylactically.
- 17. A therapeutic preparation of a lipophilic modified hedgehog polypeptide provided in a pharmaceutically acceptable carrier and in an amount sufficient to promote survival of dopaminergic cells in a mammal.
- 18. The preparation of claim 17, wherein the lipophilic modified hedgehog polypeptide is provided in an amount sufficient to produce sufficient to promote survival of dopaminergic cells in a mammal treated with MPTP at 1 mg/kg.
- 19. The preparation of claim 18, wherein the patched antagonist is provided in an amount sufficient to produce sufficient to promote survival of dopaminergic cells in a mammal treated with MPTP at 10 mg/kg.
- 20. A method for limiting damage to neuronal cells by Parkinsonian conditions, comprising administering to a patient a lipophilic modified hedgehog polypeptide.
- 21. A therapeutic preparation of a lipophilic modified hedgehog polypeptide provided in a pharmaceutically acceptable carrier and in an amount sufficient to promote survival of, or enhance functional performance of exotoxin-sensitive neuronal cells in a mammal.
RELATED APPLICATIONS
[0001] The present application is a continuation-in-part of U.S. Ser. No. 09/238,243, filed 27 Jan. 1999, the specification of which is incorporated by reference herein.
Continuations (1)
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Number |
Date |
Country |
Parent |
09325602 |
Jun 1999 |
US |
Child |
10665923 |
Sep 2003 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09238243 |
Jan 1999 |
US |
Child |
09325602 |
Jun 1999 |
US |