Phosphatonin-related gene and methods of use thereof

• US 20020115627A1
• Filed: 07/19/2001
• Published: 08/22/2002
• Est. Priority Date: 07/19/2000
• Status: Abandoned Application

• Current Assignee: Johns Hopkins University, Genzyme Corporation (Sanofi )
• Original Assignee: Johns Hopkins University
• Inventors: Schiavi, Susan, de Beur, Suzanne Jan, Madden, Stephen L., Levine, Michael, Manavalan, Parthasarathy
• Application Number:
  US09/909,775
• Publication Number:
  US 20020115627A1
• Time in Patent Office: Days
• US Class Current: 514/44
• 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: 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: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 3/12 for electrolyte homeostasis
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: C07K 14/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

This invention provides methods for modulating phosphate homeostasis and renal phosphate transport by delivering agents that alter the expression of the FRP-4 gene or alter the activity of the FRP-4 protein. The methods of the invention are useful for modulating bone mineralization, renal phosphate transport, alleviating oncogenic osteomalacia-associated symptoms and treating phosphate homeostasis-related disease. The invention further provides methods for reducing phosphate re-absorption by delivering to a subject FRP-4 protein or polynucleotides that encode this protein. In addition, the invention provides methods for detecting and monitoring expression of the FRP-4 gene and modulating the phenotype of a neoplastic cell associated with oncogenic osteomalacia. Finally, the invention provides methods for screening candidate agents to identify compositions that modify the activity of the FRP-4 gene and protein.

Claims

1. A method of modulating phosphate homeostasis in a subject comprising altering the activity of a polypeptide encoded by the FRP-4 gene within the subject.

2. The method of claim 1, wherein phosphate homeostasis is modulate by delivering to the subject an effective amount of an agent that alters the activity of a polypeptide encoded by the FRP-4 gene.

3. A method of modulating phosphate homeostasis in a subject comprising altering the expression of a polynucleotide encoding FRP-4 polypeptide within the subject.

4. A method for modulating renal phosphate transport in a subject, comprising delivering to the subject an effective amount of an agent that alters the activity of a polypeptide encoded by the FRP-4 gene.

5. A method of reducing phosphate re-absorption in a subject comprising delivering to the subject an effective amount of the FRP-4 protein.

6. A method of reducing phosphate re-absorption in a subject comprising delivering to the subject an effective amount of a polynucleotide encoding the FRP-4 protein.

7. A method of screening for candidate therapeutic agents that modulate the expression of the FRP-4 gene comprising contacting a target cell with a test agent and monitoring expression of the FRP-4 gene, wherein a test agent which modifies the expression of the FRP-4 gene is a candidate therapeutic agent.

8. The method of claim 7, wherein the candidate agent is a biological or chemical compound selected from the group consisting a polypeptide, a polynucleotide, a ribozyme, and a small organic molecule.

9. A method of screening for candidate agents capable of altering the biological activity of a polypeptide encoded by the FRP-4 gene, comprising contacting a target cell expressing a FRP-4 polypeptide with a test agent and monitoring activity of the expressed polypeptide product, wherein a test agent which modifies the activity of the polypeptide is a candidate agent.

10. The method of claim 9, wherein the candidate agent is a biological or chemical compound selected from the group consisting of a polypeptide, a polynucleotide, a ribozyme, or a small organic molecule.

11. A method of screening for candidate agents that modulate the activity of the FRP-4 protein comprising contacting a target cell with a candidate agent and monitoring the activity of the FRP-4 protein, wherein a candidate agent which modifies the activity of the FRP-4 protein is a candidate therapeutic agent.

12. The method of claim 11, wherein the candidate agent is a biological or chemical compound selected from the group consisting of a polypeptide, a polynucleotide, a ribozyme, or a small organic molecule.

14. The method of claim 13, wherein the candidate agent is a biological or chemical compound selected from the group consisting of a polypeptide, a polynucleotide, a ribozyme, or a small organic molecule.

13. A method of screening for candidate ligand that modulate the activity of the FRP-4 protein comprising contacting a target cell with a candidate agent and monitoring the activity of the FRP-4 protein, wherein a candidate agent which modifies the activity of the FRP-4 protein is a candidate ligand.