Use of p97 and iron binding proteins as diagnostic and therapeutic agents

An isolated soluble p97 which is hydrophilic.

A method for treating conditions involving disturbances in iron metabolism comprising administering an iron modulating amount of p97 or a stimulant, agonist or antagonist of p97.

A method for treating conditions involving disturbances in iron metabolism comprising administering an iron modulating amount of p97, or a stimulant, agonist or antagonist thereof.

A method for identifying a stimulant, agonist or antagonist of p97-mediated iron uptake comprising:

• incubating a cell expressing p97 on its surface and a substance suspected of being a stimulant, agonist or antagonist of p97 in the presence of iron and in the absence of transferrin, measuring the amount of iron uptake into the cell and identifying a stimulant, agonist or antagonist of p97-mediated iron uptake by comparing the amount of iron uptake in the cell with the amount of iron uptake in a cell from a control incubation in the absence of the substance.

A composition for delivering an agent across the blood brain barrier comprising p97 conjugated to the agent, a substance which is capable of specifically binding to p97 conjugated to the agent, or a p97 fusion protein containing p97 or the N-terminal or C-terminal portion of p97 sequence fused to the agent, and a pharmaceutically acceptable carrier or diluent.

A method for diagnosing or monitoring Alzheimer's Disease in a patient, comprising determining the concentration of p97 in a sample from the patient and comparing the determined concentration to the level of p97 in other samples from the patient, control subjects and/or Alzheimer Disease patients.

A method for monitoring Alzheimer's Disease, comprising detecting the presence of transferrin receptors, detecting the presence of p97 on microglial cells associated with amyloid plaques in a patient or detecting the presence of p97 in serum or cerebrospinal fluid.

A method for treating Alzheimer's Disease in a patient comprising administering p97, transferrin, transferrin receptor, antibody specific to p97 or transferrin receptor, or an iron chelator to deplete iron in the brain of the patient.

A method for treating Alzheimer's Disease comprising the step of administering to a patient p97, transferrin receptor, or a substance which is capable of binding to p97 or labelled transferrin receptor which are labelled with a substance having therapeutic activity or a toxin.