Background:
In people with multiple sclerosis (MS), brain and cerebrospinal fluid (CSF) biomarkers indicate inflammation or disease. Researchers want to see if 4 drugs given alone or combined affect MS biomarkers. They want to see if a change in biomarker levels can predict which drugs a person with MS might respond to.
Objective:
To see if signs of inflammation in CSF help predict a person s response to different drugs.
Eligibility:
People ages 18 and older who:
* Are in protocol 09-I-0032 * Have progressive MS * Can stand and walk a few steps * Take an MS drug
Design:
Participants will be screened in protocol 09-I-0032.
Participants will take 1 of the 4 study drugs. Researchers will call after 1 month to see how they are doing. Some will start a second drug. They may take each drug or combination for up to 18 months.
Participants will have 2 visits a year for up to 6 years. Visits include:
* Medical history * Physical exam * Blood and heart tests * X-rays and scans * Eye exam and tear collection * Lumbar puncture: A needle inserted between back bones removes some CSF. * Lymphocytapheresis: Blood is removed through a needle in one arm and run through a machine. The blood is returned through a needle in the other arm. * A sensor on the forehead records blood flow and oxygen use. * Participants may get a device for testing at home.
Participants will stop taking the drugs if they have taken 2 drugs together for 18 months or if they do not do well on the drugs.
Participants will be called 3 months later to see how they are doing.
Enrolled in 09-I-0032 protocol.
Clinically definite MS.
Age >=18 years at time of study enrollment.
Expanded Disability Status Scale (EDSS) 1.0-7.5.
Clinically significant medical disorders that, in the judgment of the investigators, could expose the patient to undue risk of harm or prevent the patient from safely completing all required elements of the study (such as, but not limited to significant cerebrovascular disease, ischemic cardiomyopathy, clotting disorder, other neurodegenerative disorder, substance abuse or significant psychiatric disorder such as depression with suicidal ideations, unable to perform or tolerate MRI examinations).
Clinically significant medical disorders, other than MS that require chronic treatment with immunosuppressive or immunomodulatory agents.
Pregnancy or breastfeeding.
Serum alanine transaminase or aspartate transaminase levels which are greater than three times the upper limit of normal values.