title: Mimotopic peptide immunotherapy for the treatment of multiple sclerosis, an inflammatory autoimmune disease.
abstract: Several lines of evidence suggest that mast cells play a key role in the pathogenesis of Multiple Sclerosis (MS). The contribution of mast cells likely depends upon specific adherence to myelin surface-bound IgE, which triggers degranulation and the release of enzymes that damage central nervous system (CNS) neurons. To block mast cell degranulation, a peptide-based system was developed to neutralize endogenous, myelin-targeting autoantibodies, thus halting the pathological autoimmune process. Development of the MS therapeutic involved: (1) identification of relevant myelin epitopes; (2) estimation of endogenous autoantibody quantities to be neutralized; (3) synthesis of epitope mimicking/autoantibody-neutralizing peptides; (4) subcutaneous administration of the peptides; and (5) assessment, over time, of clinical presentation together with matching, residual autoantibody levels. An open label, interventional study was performed involving a single MS patient and five control subjects as a first step towards a potentially larger, more elaborate investigation. The study encompassed serological testing to confirm the IgE-positive status of the MS patient and negative status of the controls, an eight month course of peptide-based immunotherapy, and assessment of therapeutic efficacy and potentially adverse effects. Treatment of the MS patient with the peptide-based therapy resulted in a reduction in myelin-specific IgE titers and marked clinical improvement. No subjects experienced adverse effects. Thus, peptide-based immunotherapy could provide improved clinical status or life-long remission to MS patients. Substantiation of this premise requires a follow-up examination by other investigators and institutions with larger and more extensive clinical trials.
authors.affiliation: Enteron 7030 Lattimore Drive, Dallas, TX 75252, USA.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Calenoff
keywords: Immunoglobulin E; axons; enzymology; mast cell degranulation; myelin sheath