Diagnostic and therapeutic use of a sulfotransferase for neurodegenerative diseases

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

• (i) 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 a cytosolic sulfotransferase family 4A member 1, and
• (ii) 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 a cytosolic sulfotransferase family 4A member 1 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, said kit comprising:
• at least one reagent which is selected from the group consisting of
• (a) reagents that selectively detect a transcription product of a gene coding for a cytosolic sulfotransferase family 4A member 1 and
• (b) reagents that selectively detect a translation product of a gene coding for a cytosolic sulfotransferase family 4A member 1.

A method of treating or preventing a neurodegenerative disease in a subject comprising administering to said subject in a therapeutically or prophylactically effective amount an agent or agents which directly or indirectly affect an activity and/or a level of

• (i) a gene coding for a cytosolic sulfotransferase family 4A member 1, and/or
• (ii) a transcription product of a gene coding for a cytosolic sulfotransferase family 4A member 1, and/or
• (iii) a translation product of a gene coding for a cytosolic sulfotransferase family 4A member 1, and/or
• (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 a cytosolic sulfotransferase family 4A member 1,
• (ii) a transcription product of a gene coding for a cytosolic sulfotransferase family 4A member 1,
• (iii) a translation product of a gene coding for a cytosolic sulfotransferase family 4A member 1, 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 a cytosolic sulfotransferase family 4A member 1,
• (ii) a transcription product of a gene coding for a cytosolic sulfotransferase family 4A member 1,
• (iii) a translation product of a gene coding for a cytosolic sulfotransferase family 4A member 1, 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) or (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 for inhibition of binding between a ligand and a cytosolic sulfotransferase family 4A member 1 protein, or a fragment, or derivative, or variant thereof, said assay comprising the steps of:

• (i) adding a liquid suspension of said cytosolic sulfotransferase family 4A member 1 protein, or a fragment, or derivative, or variant thereof, to a plurality of containers;
• (ii) adding a compound or a plurality of compounds to be screened for said inhibition of binding to said plurality of containers;
• (iii) adding a detectable ligand to said containers;
• (iv) incubating the liquid suspension of said cytosolic sulfotransferase family 4A member 1 protein, or said fragment, or derivative, or variant thereof, and said compound or compounds, and said ligand;
• (v) measuring amounts of detectable ligand associated with said cytosolic sulfotransferase family 4A member 1 protein, or with said fragment, or derivative, or variant thereof;
• and
• (vi) determining the degree of inhibition by one or more of said compounds of binding of said ligand to said cytosolic sulfotransferase family 4A member 1 protein, or said fragment, or derivative, or variant thereof.