Dopaminergic neurotrophic factor for treatment of Parkinson's disease

• US 5,215,969 A
• Filed: 12/09/1991
• Issued: 06/01/1993
• Est. Priority Date: 08/11/1989
• Status: Expired due to Fees

• Current Assignee: Hahnemann University
• Original Assignee: Hahnemann University, University of Rochester
• Inventors: Collier, Timothy J., Springer, Joe E.
• Primary Examiner(s): Wityshyn, Michael G.
• Assistant Examiner(s): KOH, CHOON P
• Application Number:
  US07/804,340
• Time in Patent Office: 540 Days
• Field of Search: 514/2, 514/21
• US Class Current: 514/8.4
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators

Abstract

Dopaminergic Neurotrophic Factor (DNTF), derived from cells of the peripheral nervous system, is administered to patients suffering from Parkinson'"'"'s Disease in an amount effective to facilitate survival of substantia nigra dopamine nerve cells.

Claims

1. A purified form of soluble dopaminergic neurotrophic factor derived from cultured cells of the mammalian peripheral nervous system, said factor comprising a polypeptide of molecular weight between about 9,000 and about 10,000 daltons, said factor being capable of increasing the survival time of fetal, non-mitotic dopamine nerve cells in culture, and of increasing in vivo expression of tyrosine hydroxylase in substantia nigra dopamine nerve cells exposed to said factor, said factor having a neurotrophic effect on substantia nigra dopamine nerve cells.

2. A factor as claimed in claim 1, having a molecular weight of about 9,500 daltons.

3. A factor as claimed in claim 2, wherein the N-terminal portion of said polypeptide comprises the amino acid sequence ID No. 1:

Xaa-Glu-Asp-Thr-Ser-Asn-Ile-Ala-Val-Ala-Ser-Gly-Xaa-Xaa-Pro, wherein Xaa represents an amino acid of mammalian proteins.

4. A factor as claimed in claim 1, derived from Schwann cells.

5. A factor as claimed in claim 1, which is derived via recombinant DNA techniques.

6. A pharmaceutical preparation for the treatment of Parkinson'"'"'s Disease which comprises, as an active ingredient, a purified form of soluble dopaminergic neurotrophic factor derived from cultured cells of the mammalian peripheral nervous system, said factor comrpising a polypeptide of molecular weight between about 9,000 and about 10,000 daltons, said factor being capable of increasing the survival time of fetal, non-mitotic dopamine nerve cells in culture, and of increasing in vivo expression of tyrosine hydroxylase in substantia nigra dopamine nerve cells exposed to said factor, said factor having a neurotrophic effect on substantia nigra dopamine nerve cells, and a biologically acceptable medium.

7. A pharmaceutical preparation as claimed in claim 6 wherein said biologically acceptable medium is a liquid in which said active ingredient is soluble.

8. A method for treating patients having Parkinson'"'"'s Disease, which comprises administering to said patients the pharmaceutical preparation of claim 6.

9. A method as claimed in claim 8, wherein said pharmaceutical preparation is administered by introduction into the central nervous system of said patients.

10. A method as claimed in claim 9 wherein said pharmaceutical preparation is administered by intracerebroventricular infusion.

11. A purified form of soluble dopaminergic neurotrophic factor derived from cultured cells of the mammalian peripheral nervous system, said factor comprising a polypeptide, the N-terminal portion of said polypeptide having the amino acid sequence ID No. 1:

Xaa-Glu-Asp-Thr-Ser-Asn-Ile-Ala-Val-Ala-Ser-Gly-Xaa-Xaa-Pro, wherein Xaa represents an amino acid of mammalian proteins, said factor being capable of increasing the survival time of fetal, non-mitotic dopamine nerve cells in culture, and of increasing in vivo expression of tyrosine hydroxylase in substantia nigra dopamine nerve cells exposed to said factor, said factor having a neurotrophic effect on substantia nigra dopamine nerve cells.

12. A factor as claimed in claim 11, having a molecular weight between about 9,000 and about 10,000 daltons.