Lectures: Treatment Options - Medications on the Horizon
T-Cell Receptor Peptide Immunization
Anti-CD4 Monoclonal Antibody
Intravenous Immunoglobulin G
Copolymer-1 is a randomized polymer of basic amino acids. This polymer is structurally similar to myelin basic protein. Therefore, administration of Copolymer may interfere with formation of trimolecular complex and could potentially prevent the auto immunologic cascade. This medication requires daily subcutaneous administration and decreases the frequency of relapses in patients with relapsing-remitting disease. Chronic Progressive disease does not respond to therapy with Copolymer-1. Copolymer-1 and interferon are acting through different mechanisms, and combined therapy with the two medications may be feasible.
Some data suggests that certain T-cell receptor configurations are involved in the immune response of acute demyelinating lesion. If these sequences can be identified, then they can be synthesized in vitro and injected into patients, creating an immune response against specific TCRs. If TCRs are blocked by the antibodies, then their interaction with antigen and resulting destruction of myelin will also be suppressed. Some preliminary clinical trials have been conducted. They indicated that TCR peptides can indeed induce an immune response and can be safely administered. Further investigations are needed in this area.
Anti CD4 Monoclonal Antibody Treatment
Anti CD4 monoclonal antibody treatment can be of interest because CD4s are essential components of the activated helper T-cells and thus - of a trinucleotide complex. This specific immuno-modulating treatment may be able to interfere with formation of this complex and with subsequent myelin destruction. Preliminary clinical trials showed that this treatment was well tolerated by patients with chronic progressive MS.
Being a purine analog, Azathioprine (Imuran) interferes with DNA synthesis and has numerous non-specific effects on immune system. For instance, it is known to suppress cell-mediated hypersensitivity reactions and is cytotoxic to NK lymphocytes. Imuran is cautiously used in treatment of chronic progressive disease with modest success. It has been shown to stabilize the condition in some patients. Treatment may be associated with significant side effects including nausea, hepatotoxicity, rashes and pancytopenia. It may also increase the risk of malignancies in patients.
Cyclophosphamide (Cytoxan) is another cytotoxic agent which causes a generalized immuno-suppression. It is a controversial treatment because of significant side effects, i.e.,. Hemorrhagic cystitis, alopecia, sterility, pancytopenia and increased risk for neoplasms. It has been tried in patients with chronic progressive MS, who were non responsive to steroid medications.
Oral myelin administration has been tested in clinical trials. The effect of the drug was observed in only one subgroup of patients - DR2 negative males. Significance of this observation is yet to be explained.
Methotrexate is being studied on patients with chronic progressive disease. This medication is generally used with success in patients with psoriasis, rheumatoid arthritis, and Crohn's disease and appears to be helpful for patients with advanced disease, but further clinical trials are needed.
Cladribine appears to have a relatively selective toxicity for lymphocytes. If administered intravenously, this drug appears to alter progression of MS, but more information is needed to draw conclusions.
IVIG is now being assessed in clinical trials for possible efficacy in patients with relapsing-remitting disease. Very little information is available on the potential benefits of this medication.