Researchers at Stanford University School of Medicine andImmuLogic Pharmaceutical Corp., both in Palo Alto, Calif., havedevised a way to prevent and possibly treat multiple sclerosis(MS) in animal models.
Amitabh Gaur, Garrison Fathman and their associates reportedin last Friday's issue of Science that they can preventexperimental autoimmune encephalomyelitis (EAE), the mouseequivalent of MS, in susceptible animals by inducing toleranceto fragments of myelin, the protein that forms a protectivecoating around nerve cells, and which is the target of theimmune system attack (via inducer T cells) characteristic ofMS.
Researchers induce EAE in susceptible mice by immunizingthem with myelin basic protein (MBP) or smaller peptidefragments of it that constitute MBP's immunodominant T celldeterminants. But the peptide fragments can also beadministered to mice in such a way that they induce tolerancerather than immunogenicity. This depends on several factors,including the route of administration and whether or not thepeptide is in an aggregated form, Fathman explained. Now, ifthe mice are challenged with MBP, they don't come down withEAE. In other words, peptide-specific tolerance can preventdisease -- and it may be able to treat it, as well. The Stanfordand ImmuLogic scientists have also determined that in micethis approach can block the progression and lessen the severityof disease-in-progress.
This peptide-based approach is very specific. "It inactivatesonly the T cells that recognize and respond to the myelin basicprotein, in contrast to other experimental therapeuticapproaches that paralyze broader groups of immune-reactivecells and leave the body more vulnerable to infections,"Fathman said.
These experiments represent a "proof-of-concept," said JohnFiddes, ImmuLogic's vice president of research. For ImmuLogic,the experiments "tie into the approach we're taking intolerizing to autoimmune diseases," Fiddes told BioWorld.
Whether the tolerizing approach works in humans is not yetknown.
ImmuLogic's (NASDAQ:IMUL) stock closed Wednesday at $15,up $1.75 a share.
-- Jennifer Van Brunt Senior Editor
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