Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 688-697 |
| Number of pages | 10 |
| Journal | Multiple Sclerosis |
| Volume | 12 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 1 2006 |
| Externally published | Yes |
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Keywords
- Experimental autoimmune encephalomyelitis
- Immunology
- Matrix metalloproteinase
- Multiple sclerosis
- Protease inhibitor
- Therapies
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
Cite this
The protease inhibitor, Bowman-Birk Inhibitor, suppresses experimental autoimmune encephalomyelitis : A potential oral therapy for multiple sclerosis. / Gran, Bruno; Tabibzadeh, N.; Martin, A.; Ventura, E. S.; Ware, J. H.; Zhang, G. X.; Parr, J. L.; Kennedy, A. R.; Rostami, A. M.
In: Multiple Sclerosis, Vol. 12, No. 6, 01.12.2006, p. 688-697.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The protease inhibitor, Bowman-Birk Inhibitor, suppresses experimental autoimmune encephalomyelitis
T2 - A potential oral therapy for multiple sclerosis
AU - Gran, Bruno
AU - Tabibzadeh, N.
AU - Martin, A.
AU - Ventura, E. S.
AU - Ware, J. H.
AU - Zhang, G. X.
AU - Parr, J. L.
AU - Kennedy, A. R.
AU - Rostami, A. M.
PY - 2006/12/1
Y1 - 2006/12/1
N2 - 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.
AB - 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.
KW - Experimental autoimmune encephalomyelitis
KW - Immunology
KW - Matrix metalloproteinase
KW - Multiple sclerosis
KW - Protease inhibitor
KW - Therapies
UR - http://www.scopus.com/inward/record.url?scp=33846321902&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846321902&partnerID=8YFLogxK
U2 - 10.1177/1352458506070769
DO - 10.1177/1352458506070769
M3 - Article
C2 - 17262995
AN - SCOPUS:33846321902
VL - 12
SP - 688
EP - 697
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
SN - 1352-4585
IS - 6
ER -