Methods to protect against and treat multiple sclerosis
The invention provides epsilon toxin (ETX) produced by Clostridium perfringens type B or type D as a causative toxin for human multiple sclerosis (MS). The invention further identifies ETX binding receptor MAL for ETX mediated cell death and other toxin-logical activities in MS. Methods and compositions to prevent humans from multiple sclerosis (MS) and/or treating MS by directly or indirectly interfering with epsilon toxin (ETX), its binding receptor (e.g., MAL), or ETX-receptor interactions so as to inhibit or suppress downstream ETX mediated receptor signaling activities are provided. Also provided are various methods to detect, diagnose, monitor, assess multiple sclerosis (MS) by determining an expression level of ETX gene or its encoding protein in human patient suspected for and/or at risk for multiple sclerosis (MS).
1. A method for treating epsilon toxin induced neurologic symptoms of multiple sclerosis (MS) in a subject in need comprising: administering to said subject a composition comprising an effective amount of an antibody that inhibits epsilon toxin (ETX) receptor from binding to Epsilon or ETX oligomerization, wherein the epsilon toxin (ETX)-produced by Clostridium perfringens type B or type D bacterial strain, so as to inhibit or suppress ETX modulated receptor signaling activities, and wherein said ETX-binding receptor is a tetraspan integral membrane receptor MAL or HAVcR-1 receptor, thereby treating neurologic symptoms of MS in said subject.
2. The method of claim 1 , wherein said antibody is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, and a recombinant antibody.
3. The method of claim 2 , wherein said antibody is human or humanized antibody.
4. The method of claim 1 , wherein said antibody is a neutralizing antibody against ETA or a functional component thereof.
5. The method of claim 1 , wherein said ETX-binding receptor is expressed on endothelial cells of blood brain barrier (BBB) for which ETX is a ligand.