We know that about 400,000 people in the United States currently suffer from multiple sclerosis (MS), and it's more common in women and Caucasians. We also know that early treatment of the condition makes a difference. Recently, we've read that Biogen Idec and Elan Corp. were given the go-ahead to reintroduce natalizu-mab (Tysabri) for the treatment of relapsing forms of MS. But beyond that, we haven't heard too much lately regarding the treatment of this devastating disease. What, if anything, coming down the pipeline looks promising? Here are a few of the possibilities:
- Cladribine, from Serono, has just been granted fast-track designation by the FDA. The drug is an orally available purine nucleoside analog that interferes with the proliferation and behavior of lymphocytes involved in the pathological process of MS. A phase III trial in more than 1,200 patients over two years is evaluating endpoints, including assessments of clinical relapses, MRI brain scan, and disability progression. According to Serono, cladribine has the potential to be the first oral therapy to treat relapsing forms of MS.
- From Immune Response Corp., in collaboration with Oregon Health & Science University, is a new immune-based therapy called NeuroVax, currently in phase II trials as a potential treatment for relapsing forms of MS. The product works by stimulating a strong disease-specific, cell-mediated immunity and enhancing levels of FOXP3+ regulatory T-cells (Treg) that are able to down-regulate the activity of pathogenic T-cells that cause MS. According to the company, research has shown that low levels of FOXP3+ Treg cell responses are associated with the pathogenesis and progression of MS and other autoimmune diseases. Research has also shown that MS patients have abnormalities in FOXP3+ message and protein expression in peripheral Treg cells.
NeuroVax, administered by intramuscular injection, contains a combination of three T-cell receptor (TCR) peptides that represent immunogenic regions from TCRs that are expressed by the pathogenic T-cells in MS patients. The three peptides are BV5S2, BV6S5, and BV13S1. The firm has also developed a stable formulation of these three peptides (Incomplete Freund's Adjuvant) that, when injected, elicited a strong immune response in over 90% of the MS patients who received it. These responses to peptides are important, since clinical data show a correlation between the strength of T-cell response to TCR therapy and clinical benefit after one year of therapy.
- BHT-3009 is an antigen-specific treatment for MS from Bayhill Therapeutics. Currently in phase II trials, the drug is the first human-specific DNA plasmid for MS, according to the company. The plasmid has been designed to down-regulate rogue T cells specific for myelin basic protein (MBP). If left unchecked, these T cells shred the myelin sheath that insulates the nerve cells of the brain and spinal cord, resulting in MS. The down-regulation occurs only in the MBP-specific T cells, leaving the remainder of the immune system intact to fight infections. According to Bayhill, "BHT-3009 expresses full-length MBP, thereby encompassing all possible target autoantigens, rather than a single autoantigen, and allowing for broader possible population of responders to the drug."