Translational Research Division

Overview

Our Center has a distinguished record and a long history of optimizing treatment for patients with MS. Over the years our innovative treatments have included being the first in New York City to use intrathecal (IT) baclofen (ITB) for spasticity in 1992. Later, we published original work on the use of ITB in ambulatory patients with MS (2006), IT morphine (2009) and IT clonidine (2012) for intractable pain and spasticity cases. Specifically, for the progressive forms of MS, we were the first in the world to use intrathecal methotrexate (J of Neurology 2010) and currently have treated approximately 500 patients with an excellent safety record.

Strategy

In 2002, we initiated a biomarker discovery program to better understand the pathology of the disease. We first showed that CSF osteopontin levels correlate with disease severity and progression (Arch. Neurol. 2008). Later, Dr. Violaine Harris showed that Bri 2-23 protein levels in CSF were a marker of cerebellar disease and cognition disease (Neurobio. Dis 2010). Extensive work with Fetuin-A levels in CSF has established that it is a biomarker of disease activity in MS, work which we have patented and published (Multiple Sclerosis J 2013).

Finally, work by Dr. Fozia Mir has identified CSF lipid peroxidation products as reliable biomarkers of Central Nervous System (CNS) oxidative stress in patients with MS (patent application pending; manuscript in preparation). Furthermore, we have performed detailed cell analysis on the CSF of several hundred patients which allows us to determine the ratio of T-cells, B-cells and other inflammatory cells in an individual patient.

Implications for MS Patients

All of these research advances are practical and relevant to MS patients. This form of detailed analysis of CSF is only available at our Center. Using CSF analysis, we can determine in a challenging patient how active the disease is (Fetuin A level), how likely is it to progress (osteopontin), and the level of oxidative stress (lipid peroxidation levels) in the patient. Together with the cell analysis, we can rationally decide on which treatment is most likely to be effective and how potent or aggressive a therapy is needed.

Such biomarker based profiling in optimizing treatment for MS is predicted to become widely practiced in the future and we at Tisch MSRCNY are already there leading the way.