Methods for diagnosis and optimizing treatment of multiple sclerosis
Biological markers for multiple sclerosis, and their use in the diagnosis and prognosis of the disease, are described. Also described are methods for treating multiple sclerosis by administering an inhibitor of cathepsin B activity or a neuroprotective composition comprising a modified terpenoid compound. Also described are isolated polypeptide biomarkers, polynucleotides encoding the polypeptide biomarkers, and antibodies that bind specifically to the polypeptide biomarkers. Further described are kits that include the above-mentioned isolated polypeptide biomarkers, the polynucleotides encoding them, or specific antibodies against the polypeptide biomarkers.
1. A method for diagnosis 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 8 amino acids at its C-terminus; and (ii) determining the ratio of the fragment to full length cystatin C protein in the biological sample; and (iii) comparing the ratio obtained in (ii) with a corresponding control ratio determined from a control subject; wherein a ratio determined in step (ii) that is greater than the control ratio indicates a diagnosis of multiple sclerosis.
2. The method of claim 1 , wherein the biological sample is a cerebrospinal fluid or blood sample.
3. The method of claim 1 , wherein the determining comprises performing mass spectroscopy on the biological sample and indicating the peak corresponding to the cystatin C protein fragment and the peak corresponding to the full length cystatin C protein.
4. The method of claim 1 , that further comprises performing a cathepsin B activity assay on at least a fraction of the biological sample.
5. A method for optimizing multiple sclerosis treatment of a subject in need thereof, that comprises (i) obtaining a first biological sample from the subject; (ii) determining the ratio of the level of a cystatin C protein fragment lacking 8 amino acids at its C terminus to the level of full length cystatin C protein in the first biological sample; (iii) providing a multiple sclerosis treatment to the subject; (iv) obtaining a second biological sample from the subject; (v) determining the ratio of the fragment to the full length cystatin C protein in the second biological sample; and (vi) 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.