Methods and Compositions for Diagnosis and Treatment of Multiple Sclerosis

A method for diagnosis or prognosis of multiple sclerosis in a subject, that comprises (i) determining in a biological sample from the subject the level of full length cystatin C protein and the level of a cystatin C protein fragment lacking about 8 amino acids at its C-terminus;

• (ii) determining the ratio of the fragment to full length cystatin C protein in the biological sample;
• and (iii) providing the value of the ratio to a medical caregiver for the subject.

A method for optimizing multiple sclerosis treatment of a subject in need thereof, that comprises providing a multiple sclerosis treatment to the subject, comparing the ratio of a cystatin C protein fragment lacking about 8 amino acids at its C terminus to full length cystatin C protein in a first biological sample obtained from the subject prior to the treatment to the ratio of the cystatin C protein fragment lacking about 8 amino acids at its C terminus to the full length cystatin C protein in a second biological sample obtained from the subject after the beginning of the treatment, and altering the treatment if the ratio in the second biological sample is greater than the ratio in the first biological sample;

• or maintaining the treatment unaltered if the ratio in the second biological sample is equal to or less than the ratio in the first biological sample.

A method for treating or preventing MS or a condition relating thereto in a subject, that comprises administering to a subject in need thereof a therapeutically effective amount of an agent that decreases cathepsin activity.

An isolated antibody that binds specifically to an epitope in the last 8 amino acids of the cystatin C protein C-terminus, and does not bind significantly to the full-length C-protein.

An isolated antibody that binds specifically to a cystatin C protein fragment lacking about 8 amino acids at its C-terminus, and does not bind significantly to a full-length cystatin C protein.