title: The MSMV hypothesis: measles virus and multiple sclerosis, etiology and treatment.
abstract: Multiple sclerosis (MS) is a progressive disease characterised by periods of quiescence and exacerbation. It is found more often in northern and southern climates, rather than those closer to the equator, where it is especially rare, and, therefore, cannot be considered as an autoimmune disease. We present the MSMV Hypothesis, involving novel ideas which encompass an understanding of the blood brain barrier (BBB) function, the lymphocyte population, together with the viral presence in the CNS of what we are calling the multiple sclerosis measles virus (MSMV) that is the immediate cause of MS, and which exhibits a similar immunologic response of the systemic virus. We assume that the geographical distribution of MS is related to MSMV's sensitivity to ultraviolet light and that it is feasible to assume a viral etiology for MS based on this. The methodology employed is eclectic and grounded on several differing approaches: involved are the meta-analyses of two comprehensive studies on the effects of azathioprine in the treatment of a large number of MS patients undertaken since the early 1990s, a pioneering pilot study that examined the effects of azathioprine treatment on a smaller set of patients in the late 1960s; and, finally, we also outline the results of several experiments in cell culture on two MV strains using a new drug lead that has been shown to effectively stave off the progression of MS by interfering with the normal replication process of the MSMV. In the latter case, strain Edmonston (MV-E) was employed, along with strain Halle (MV-H), which was obtained from a lymph node of a patient with subacute sclerosing panencephalitis (SSPE), which mimics various aspects of the pathology of neurological diseases, including demyelination. An analogue of a metabolite of azathioprine (ESP) was evaluated for antiviral activity against these two viral strains. The results proved positive for the MV-H infected cells as syncytia formation was reduced in a dose-dependent manner, and under protocols which avoided toxic effects, following ESP treatment ranging from 66% with 1 microg/ml and to 25% with 0.1 microg/ml. Since ESP is an analogue of the active metabolite of azathioprine, which exhibits positive outcomes when administered to MS patients, we submit that this metabolite is acting on MSMV, in a similar fashion to the action of ESP on MV-H.
authors.affiliation: Biomolecular Pharma Inc., 12 West Street, Charlottetown, Prince Edward Island, Canada C1A 3S4. william.tucker@biomolecularpharma.com
authors.forename: William G
authors.initials: WG
authors.lastname: Tucker
authors.forename: R
authors.initials: R
authors.lastname: Andrew Paskauskas
mesh_terms: D001379:Azathioprine / Q000494:pharmacology; D001812:Blood-Brain Barrier; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D008457:Measles / Q000209:etiology* / Q000628:therapy* / Q000821:virology; D008459:Measles virus / Q000378:metabolism*; D008954:Models, Biological; D008962:Models, Theoretical; D009103:Multiple Sclerosis / Q000209:etiology* / Q000628:therapy* / Q000821:virology; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D001379:Azathioprine