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Am J Clin Exp Immunol 2013;2(3):208-221
Original Article
Mimotopic peptide immunotherapy for the treatment of multiple sclerosis,
an inflammatory autoimmune disease
Emanuel Calenoff
Enteron, 7030 Lattimore Drive, Dallas, TX 75252, USA
Received June 26, 2013; Accepted October 7, 2013; Epub October 16, 2013; Published October 30, 2013
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. (AJCEI1305004).
Keywords: Immunoglobulin E, mast cell degranulation, enzymology, myelin sheath, axons
Address correspondence to: Dr. Emanuel Calenoff, Enteron, 7030 Lattimore Drive, Dallas, TX 75252, USA. Tel:
1-510-682-6013; Fax: 1-972-380-0083; E-mail: ecalenoff@earthlink.net
Original Article
Mimotopic peptide immunotherapy for the treatment of multiple sclerosis,
an inflammatory autoimmune disease
Emanuel Calenoff
Enteron, 7030 Lattimore Drive, Dallas, TX 75252, USA
Received June 26, 2013; Accepted October 7, 2013; Epub October 16, 2013; Published October 30, 2013
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. (AJCEI1305004).
Keywords: Immunoglobulin E, mast cell degranulation, enzymology, myelin sheath, axons
Address correspondence to: Dr. Emanuel Calenoff, Enteron, 7030 Lattimore Drive, Dallas, TX 75252, USA. Tel:
1-510-682-6013; Fax: 1-972-380-0083; E-mail: ecalenoff@earthlink.net
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