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The protease inhibitor, Bowman-Birk Inhibitor, suppresses experimental autoimmune encephalomyelitis: a potential oral therapy for multiple sclerosis

Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA, Division of Clinical Neurology, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham, UK, bruno.gran{at}nottingham.ac.uk

N Tabibzadeh

Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA

A Martin

Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA

E S Ventura

Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA

J H Ware

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA

G-X Zhang

Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA

J L Parr

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

A R Kennedy

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA

A M Rostami

Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA, a.m.rostami{at}jefferson.edu

Available treatments for multiple sclerosis (MS) require frequent injections and have significant side effects. Proteases generated during inflammation are involved in the induction of tissue damage during inflammatory demyelination in the central nervous system (CNS). The Bowman-Birk Inhibitor (BBI), a soy-derived protease inhibitor with anti-carcinogenic and anti-inflammatory properties, has been shown to be well tolerated in clinical trials for pre-cancerous conditions, such as oral leukoplakia and the inflammatory disease, ulcerative colitis. We hypothesized that BBI may modulate experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The BBI concentrate (BBIC), a soybean extract enriched in BBI, was administered to myelin basic protein (MBP)-immunized Lewis rats by gastric gavage in different treatment regimens, during the induction or the effector phase of disease. BBIC significantly delayed disease onset and suppressed disease severity, clinically and pathologically, in all treatment protocols. Both in vitro and ex vivo, BBIC inhibited MBP-specific proliferation of lymph node cells. BBIC reduced the activity of matrix metalloproteinase (MMP)-2 and -9 in spleen cell supernatants and was detected in the CNS of treated rats. BBIC suppresses EAE, it can be administered orally, and it is safe and relatively inexpensive. It may have a therapeutic role in patients with MS.

Key Words: experimental autoimmune encephalomyelitis • immunology • matrix metalloproteinase • multiple sclerosis • protease inhibitor • therapies

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