Diagnostic and therapeutic use of the human hif3alpha gene and proteins for neurodegenerative diseases

A kit for diagnosing or prognosticating a neurodegenerative disease in a subject, or determining the propensity or predisposition, or the risk of a subject to develop such a disease, said kit comprising:

• at least one reagent which is selected from the group consisting of
• (i) reagents that selectively detect a transcription product of a gene coding for HIF3a and
• (ii) reagents that selectively detect a translation product of a gene coding for HIF3a;
• whereby the diagnosis or prognosis or determination of the risk to develop said neurodegenerative disease is determined by the steps of
• (a) detecting in a sample obtained from said subject a level, or an activity, or both said level and said activity of a transcription product and/or of a translation product of a gene coding for HIF3a, and
• (b) comparing said level or activity, or both said level and said activity of a transcription product and/or of a translation product of a gene coding for HIF3a to a reference value representing a known health status and/or to a reference value representing a known disease status, and said level, or activity, or both said level and said activity, of said transcription product and/or said translation product is varied compared to a reference value representing a known health status, and/or is similar or equal to a reference value representing a known disease status.

A modulator of an activity and/or of a level of at least one substance which is selected from the group consisting of

• (i) a gene coding for HIF3a,
• (ii) a transcription product of a gene coding for HIF3a,
• (iii) a translation product of a gene coding for HIF3a, and
• (iv) a fragment, or derivative, or variant of (i) to (iii).

A method for screening for a modulator of neurodegenerative diseases, or related diseases or disorders of one or more substances selected from the group consisting of

• (i) a gene coding for HIF3a,
• (ii) a transcription product of a gene coding for HIF3a,
• (iii) a translation product of a gene coding for HIF3a, and
• (iv) a fragment, or derivative, or variant of (i) to (iii), said method comprising:
• (a) contacting a cell with a test compound;
• (b) measuring the activity and/or level of one or more substances recited in (i) to (iv);
• (c) measuring the activity and/or level of one or more substances recited in (i) to (iv) in a control cell not contacted with said test compound;
• and
• (d) comparing the levels and/or activities of the substance in the cells of step (b) and (c), wherein an alteration in the activity and/or level of substances in the contacted cells indicates that the test compound is a modulator of said diseases or disorders.

A method of screening for a modulator of neurodegenerative diseases, or related diseases or disorders of one or more substances selected from the group consisting of

• (i) a gene coding for HIF3a,
• (ii) a transcription product of a gene coding for HIF3a,
• (iii) a translation product of a gene coding for HIF3a, and
• (iv) a fragment, or derivative, or variant of (i) to (iii), said method comprising:
• (a) administering a test compound to a test animal which is predisposed to developing or has already developed symptoms of a neurodegenerative disease or related diseases or disorders in respect of the substances recited in (i) to (iv);
• (b) measuring the activity and/or level of one or more substances recited in (i) to (iv);
• (c) measuring the activity and/or level of one or more substances recited in (i) to (iv) in a matched control animal which is predisposed to developing or has already developed symptoms of a neurodegenerative disease or related diseases or disorders in respect to the substances recited in (i) to (iv) and to which animal no such test compound has been administered;
• (d) comparing the activity and/or level of the substance in the animals of step (b) and (c), wherein an alteration in the activity and/or level of substances in the test animal indicates that the test compound is a modulator of said diseases or disorders.

An assay for testing a compound or a plurality of compounds to determine the degree of binding of said compounds to a HIF3a translation product, or to a fragment, or derivative, or variant thereof, said assay comprising the steps of:

• (i) adding a liquid suspension of said HIF3a translation product, or a fragment, or derivative, or variant thereof, to a plurality of containers;
• (ii) adding a detectable compound or a plurality of detectable compounds to be screened for said binding to said plurality of containers;
• (iii) incubating said HIF3a translation product, or said fragment, or derivative, or variant thereof, and said detectable compound or compounds;
• (iv) measuring amounts of detectable compound or compounds associated with said HIF3 a translation product, or with said fragment, or derivative, or variant thereof;
• and
• (v) determining the degree of binding by one or more of said compounds to said HIF3a translation product, or said fragment, or derivative, or variant thereof.