United States Patent: 6,767,564
Issued: July 27, 2004
Inventors: Rostami; Abdolmohamad (Gladwynne, PA); Kennedy; Ann R. (Wynnewood, PA)
Assignee: The Trustees of the University of Pennsylvania (Philadelphia, PA)
Appl. No.: 943688
Filed: August 31, 2001
The present invention provides a non-toxic therapy and a novel use for Bowman Birk Inhibitor (BBI), as administered in Bowman Birk Inhibitor Concentrate (BBIC), for the treatment of autoimmune diseases in a patient, wherein the disease is characterized by chronic inflammation, such as rheumatoid arthritis; and more particularly for the treatment of those diseases that are characterized by chronic neuroinflammation and/or demyelination, such as Multiple Sclerosis (MS) and Guillain Barre Syndrome (GBS). In addition, the present invention provides methods for using BBI/BBIC to reduce, inhibit, suppress or prevent the chronic inflammation in such patients; and more particularly, to reduce, inhibit, suppress or prevent the chronic neuroinflammation and demyelination that occurs when the patient's nerve tissue is affected by the disease.
SUMMARY OF THE INVENTION
The present invention provides a non-toxic therapy and a novel use for Bowman Birk Inhibitor (BBI), as administered in Bowman Birk Inhibitor Concentrate (BBIC), for the treatment of autoimmune diseases characterized by chronic inflammation in a patient, such as rheumatoid arthritis, and more particularly for the treatment of those diseases that are characterized by chronic neuroinflammation and/or demyelination, such as Multiple Sclerosis (MS) and Guillain Barre Syndrome (GBS). In addition, the present invention provides methods for using BBI/BBIC to reduce, inhibit, suppress or prevent the chronic inflammation in such patients; and more particularly, to reduce, inhibit, suppress or prevent the chronic inflammation and demyelination that occurs when the patient's nerve tissue is affected by the disease. Such neuroinflammation may affect the central nervous system or peripheral nervous system of the patient.
The method is, therefore, provided for the treatment of chronic autoimmune diseases in the patient characterized by inflammation, such as rheumatoid arthritis, and more particularly for the treatment those diseases that are characterized by neuroinflammation and/or demyelination, such as Multiple Sclerosis (MS) and Guillain Barre Syndrome (GBS).
In a preferred embodiment of the invention, the method of using BBI/BBIC to treat a disease is applied to a human patient, although other animals, particularly mammals may also be treated.
In another preferred embodiment of the invention, the method is provided in which the Bowman Birk Inhibitor is administered orally. In certain preferred embodiments, BBI/BBIC is administered to the patient with a carrier, or it is administered with another therapeutic agent, drug, medicament or treatment
In yet another preferred embodiment of the invention the method is provided in which the Bowman Birk Inhibitor (BBI) is administered as Bowman Birk Inhibitor Concentrate (BBIC). The BBI is provided as an enriched concentrate extracted from a legume, preferably as an enriched concentrate extracted from soybeans (BBIC).
Also provided in the present invention is a method for treating inflammation in an animal model of an induced inflammatory disease comprising administering to the animal an amount of Bowman Birk Inhibitor effective to reduce, inhibit, suppress or prevent the chronic inflammation. As above, the method is preferably applied when the chronic inflammation is inflammation of neural tissue, as part of either the central nervous system or the peripheral nervous system of the patient. The present method is particularly useful when used to reduce, inhibit, suppress or prevent demyelination of the nerve tissue of the patient. In a preferred embodiment of the present method, the induced disease is Experimental Autoimmune Encephalomyelitis (EAE) or Experimental Autoimmune Neuritis (EAN).
Not only does the use of BBIC, alone or in concert with other agents or treatments, provide a major step forward in the treatment of MS and other chronic inflammatory autoimmune diseases, including neuroinflammatory diseases, its use will permit further studies into the nature of the inflammatory reactions involved in such diseases. Thus, the invention further provides for the use of BBI/BBIC in vitro with cells from patients or animal subjects affected by or subject to induced inflammatory responses, such as EAE or EAN, as well as chronic inflammatory autoimmune diseases, such as rheumatoid arthritis, or chronic neuroinflammatory autoimmune diseases, such as MS and GBS.
DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION
The invention provides a novel method for the use of BBI/BBIC to treat patients with chronic inflammatory autoimmune disease, such as, but limited to, rheumatoid arthritis; and particularly to treat patients with diseases characterized by neuroinflammation and/or demyelination, such as, but not limited to Multiple Sclerosis (MS) and Guillain Barre Syndrome. The method of using BBI/BBIC effectively reduces, inhibits, suppresses or prevents inflammation in such a patient, and when the disease is characterized by neuroinflammation, the method of using BBI/BBIC effectively reduces, inhibits, suppresses or prevents neuroinflammation and/or demyelination of the nerve tissue of the patient.
In a preferred embodiment of the invention, the method is provided in which BBI/BBIC is used to treat an animal subject in which an inflammatory disease is induced, such as Experimental Autoimmune Encephalomyelitis (EAE) or Experimental Autoimmune Neuritis (EAN). The application of the present method of treating inflammation and neuroinflammation in such an animal subject, as displayed by the alleviation or elimination of paralysis, is also an accepted animal model for the responses found in human patients with MS, GBS, or other chronic inflammatory autoimmune diseases.
The use of BBIC for the treatment of MS according to a preferred embodiment of the present invention was selected for a combination of reasons including, but not necessarily limited to, the following. First, there exists a substantial body of evidence that demonstrates increased local protease deposition in the MS lesions, including the presence of macrophages in the cellular zone of early plaque lesions. This protease activity includes neutral serine proteases, such as plasmin, chymase and cathepsin G. Such serine proteases both have a directly damaging effect on myelin, (Romanic et al., Brain Pathol. 4:145-156 (1994)), and they convert metalloproteinase (MMP) pro-enzymes into functionally active enzymes, with potentially toxic effects.
Second, it is not yet known exactly how much BBI enters the human CNS after oral BBIC dosing. However, it is anticipated that BBI entry is increased in the CNS of patients affected by MS because of localized decreases in the blood-CNS barrier in such areas. Also, based on the background evidence reviewed above, one would also expect BBI to inhibit entry of immune/inflammatory cells into the CNS, with potential for reduction of the pathogenic effects of such cells.
Third, in preliminary studies, BBIC has been shown to be a potent inhibitor of several serine proteases. Because neutral serine proteases appear to play an important initial role in the activation of MMPs in the pro-inflammatory enzymatic cascade described above, inhibition of such serine protease activity is potentially important to the therapeutic approach in MS. As reviewed (Cuzner et al., 1999; Hartung et al., 2000), this is significant because extracellular proteolysis has been associated with several effects of importance in inflammatory demyelination, which although not intended to be limiting, include:
(1) proteolysis of myelin components, such as myelin basic protein (MBP);
(2) generation of encephalitogenic peptides which could induce autoimmune reactions;
(3) proteolysis of basement membranes, leading to increased extravasation of humoral factors and cells (decreased blood-brain barrier), implying an important role for MMP's in the process of T-cell migration into the CNS;
(4) proteolysis of the extracellular matrix-leading to enhanced inflammatory cell migration after entry into the CNS; and
(5) proteolysis of cell surface molecules on resident cells leading to cytolysis; and proteolytic activation of other zymogens.
Moreover, the therapeutic modulation of serine protease activity may be particularly important in MS because the inhibition of serine proteases by naturally occurring anti-proteinases may be impaired in MS lesional areas.
These observations are consistent with the notion that mast cell proteases also play a role in MS. If so, BBI, which is a highly effective inhibitor of cathepsin G and chymase, two of the major mast cell proteases, provides an excellent agent of intervention at this point.
BBIC administration has demonstrably inhibited both the clinical and pathologic expression of EAE and EAN, which are the recognized animal models for autoimmune disorders characterized by neuroinflammation and demyelination--MS and Gullain Barre Syndrome. Inhibition of plasmin formation and synthetic inhibitors of MMP activity have both been shown to reduce severity of clinical EAE (Cuzner et al., 1999; Gijbels et al., J. Clin. Invest. 94:2177-2182 (1994); Clements et al., J. Neuroimmunol. 74:85-94 (1997); Hewson et al., Inflamm. Res. 44:345-349 (1995)). MMP inhibitors, including naturally occurring agents such as TIMP, may be expected to work at two levels: 1) by blocking extravasations of inflammatory cells into the CNS, and 2) by inhibiting effector properties of lymphocytes and macrophages in the initial stage of inflammation in the MS lesion, without an apparent inhibitory effect on the sensitization of T cells to myelin components (Cuzner et al., 1999).
Since reactive oxygen species (ROS) can damage both oligodendroglia and myelin in CNS inflammatory reactions, inhibition of ROS formation by BBI offers another ameliorative effect in MS.
Fourth, in human trials involving patients with oral leukoplakia, benign prostatic hyperplasia, and ulcerative colitis since 1992, BBIC has not caused, or been associated, with any toxic effects or induced immune response when used at doses approximately comparable to those employed in the present invention.
Fifth, BBIC is a reasonably well-defined patented product, classified by the FDA as an Investigational New Drug for use in humans. An adequate supply of BBIC is available for studies of sufficient length to determine: a) the safety of BBIC in MS patients, and b) acquire data relating to therapeutic efficacy.
Consequently BBI/BBIC is a highly effective, non-toxic, anti-inflammatory agent useful for the treatment of MS, as well as for the treatment of EAE, an animal model directly analogous to MS. The response in BBI/BBIC treated rats with EAE is similar to the earlier demonstrated response in BBI/BBIC treated rats with EAN. The method is also highly effective for the treatment of other chronic inflammatory autoimmune diseases, such as rheumatoid arthritis, and chronic neuroinflammatory diseases, such as GBS, although the invention is not to be limited to only the identified examples.
In preferred embodiments of the invention, as set forth by Example, BBI/BBIC produced according to known methods effectively suppresses inflammation, such as that which is found associated with rheumatoid arthritis, and in particular effectively suppresses neuroinflammation of the type characteristically found in autoimmune diseases, including MS and GBS. The clinical study set forth in Example 3 is intended to exemplify the parameters of the method of using BBI/BBIC to reduce, inhibit, suppress or prevent inflammation, preferably neuroinflammation in a patient with MS, GBS or rheumatoid arthritis. However, the parameters set forth therein are intended to be exemplary, not limiting as to the dosage or treatment regime that may be used in accordance with the present methods.
By "reduce," "inhibit," "suppress" or "prevent" the chronic inflammation or neuroinflammation is meant to modulate the inflammatory or neuroinflammatory effect of the disease in a patient or animal subject affected by the disease, as compared with a matched, untreated control patient or subject when an effective amount of the BBI/BBIC is administered, such that the inflammation or neuroinflammation is measurably or visibly changed (e.g, reduced, inhibited, suppressed or prevented, as such terms are commonly understood).
In the present invention, compositions comprising BBI for the treatment of diseases or atypical inflammatory conditions are also provided, particularly for neuroinflammatory conditions involved in autoimmune disease. MS and GBS are, as previously noted, reported to be autoimmune diseases or disorders. Other such autoimmune diseases characterized by inflammation include, but are not limited to, e.g., systemic lupus erythematosis and myasthenia graves. However, in the event that MS or GBS are shown not to be autoimmune in nature, the principles set for herein for their treatment remain unchanged. In a preferred embodiment, the BBI/BBIC compositions further comprise a pharmaceutically acceptable carrier.
By "BBI" it is meant any Bowman-Birk Inhibitor or Bowman-Birk Inhibitor product, including, but not limited to, BBI prepared by methods known in the art and BBI concentrates ("BBIC") prepared in accordance with the method of U.S. Pat. No. 5,217,717. Also provided are methods of treating inflammation, particularly neuroinflammation, in an animal by administering an effective amount of a composition comprising BBI.
By "animal" is meant, but is not limited to, any mammal including humans. In the alternative, the term "patient" is also used to indicate the animal, mammal or human being treated with BBI/BBIC in accordance with the disclosure of the present invention. When animal models are treated by the present method, the term "subject" is more frequently used, rather than "patient."
It is clear from many animal studies that orally ingested BBI is absorbed and has systemic effects (reviewed in Kennedy, 1998). The structure of the BBI molecule is extremely stable, such that it survives the digestive process and appears in the colon, etc., as an intact protease inhibitor capable of inhibiting proteolytic activities (Yavelow et al., Cancer Res. 43:2454-2459 (1983); Billings et al., Canc. Lett. 62:191-197 (1992)). Many other protease inhibitors which have been studied in vivo do not survive the digestive process. Moreover, when BBI reaches the colon in intact, active form after ingestion, approximately half of ingested BBI is taken up into the bloodstream (Billings et al., 1992).
The amount of BBI taken up from the gastrointestinal tract into the blood and distributed to internal organs is such that biological effects from BBI are expected in many different organ systems. Absorbed BBI is measurable in humans (e.g., U.S. Pat. No. 5,961,980).
Antibodies to "reduced BBI" have been produced and utilized to measure blood and urine levels of BBI after the ingestion of BBIC (Wan et al., J. Immunol. Meth. 180:117-130 (1995); U.S. Pat. Nos. 5,616,492 and 5,618,679). Pharmacokinetic studies utilizing these antibodies have been performed in rodents, dogs and humans (Wan et al., unpublished data). It is also clear that BBI can be internalized by intestinal epithelial cells (Billings et al., Eur. J. Canc. 27:903-908 (1991)).
It is further known that dietary concentrations of BBIC/BBI capable of preventing cancer in animals in many different organ systems are not toxic. Yet, these same concentrations of BBI/BBIC are known to affect inflammation in animals (Kennedy, 1993A; Kennedy, 1998; Kennedy, Preventive Med. 22:796-811 (1993C); Kennedy, Cancer Res. (suppl) 54:1999s-2005s (1994); Kennedy, In Nutrients in Cancer Prevention and Treatment, Prasad (ed) 1995B, pp. 71-82).
Compared to raw soybeans, the trypsin inhibitory activity of BBIC has been greatly reduced and the chymotrypsin inhibitory activity has been increased (Kennedy, 1993B). It was, however, earlier thought that the soybean-derived protease inhibitors had the potential to inhibit the growth of young animals, and, perhaps, contribute to pancreatic cancer development in rats. However, it is now recognized by many investigators that the soybean protease inhibitors are not responsible for the growth suppressing effects of raw soybean products in young animals (Birk, In Protease Inhibitors as Cancer Chemopreventive Agents. Troll W, Kennedy A R (eds). New York, Plenum Press, 1993, pp. 97-106). When BBIC was tested at doses considerably higher than the doses of BBIC typically administered to people, significant drug induced toxicity was not observed in any organ, including the pancreas, in at least three species of animals (mice, rat, hamsters) evaluated in the Kennedy laboratory (e.g., Kennedy, 1993A), and in sub-chronic and chronic toxicity studies performed in animals (rodents, dogs) and studied at Southern Research Institute (SRI) and MPI Research, Inc. (Page et al., unpublished data (Page et al., SRI-CBE-94-135-7482 and SRI-CBE-94-060-7482, Birmingham, Ala.; Southern Research Institute, 1994; Serota, 560-057 and 560-058, MPI Research, Inc., Mattawan, Mich. (2000)).
Animal experiments at extremely high doses of BBIC have been carried out for as long as the animals' life spans. Thus, even at extremely high doses of dietary BBIC, no histopathologic alterations in the pancreas have been observed. Consequently, the assumption that the soybean protease inhibitors are involved in rat pancreatic cancer development is erroneous, as discussed extensively in, e.g., Kennedy, 1993A-C; Kennedy, 1994; Kennedy, J. Nutr. 125:733s-743s (1995C)). In human trials, no adverse effects of BBIC on the pancreas have been observed.
The possibility that soybean protease inhibitors may have impact upon the growth of the rat pancreas is triggered by the ability of the protease inhibitors to inhibit trypsin, but not chymotrypsin (Birk, 1985; Birk, 1975), while the ability to inhibit carcinogenesis, and presumably inflammation, is associated with the ability to inhibit chymotrypsin (which is why the strength of BBIC doses is measured in CI units) (Yavelow et al., 1985; Kennedy 1993B). However, the two protease inhibitor sites in BBI are separable and distant from each other in the molecule.
Although presently available in concentrates extracted from soybeans, BBI is also found in other members of the legume family of plants, such as adzuki beans, black beans, black-eyed peas, peas, lima beans, kidney beans, navy/white beans, pinto beans, chick peas, peanuts, lentils and the like. Using the methods known in the prior art for preparing the enriched BBIC concentrates from soybeans, one of ordinary skill in the art could readily prepare BBI concentrates from other legumes. Although the resulting concentrates may not have the same CI values as soybean BBIC, the key factor is that there is some degree of chymotrypsin inhibition. Thus, the resulting concentrate would be quantifiable in CI units.
On a comparable weight basis, the doses of soybean BBIC needed to prevent cancer development or have an anti-inflammatory effect, are well below the doses of soybean protease inhibitor activity associated with triggering the feedback response leading to pancreatic abnormalities (Kennedy, 1993A-C, Kennedy, 1994, Kennedy, 1995C). As a result, even on a theoretical basis, the doses of BBI/BBIC used in the treatment of MS would not create a toxicity problem in human patients.
The only toxicity which has previously been associated with BBI/BBIC treatment of animals has been that of causing toxicity to the developing embryo when injected at an extremely high level into pregnant mice (Kennedy, 1993A-C; Kennedy, 1994). At normal dosages, BBI/BBIC do not have teratogenic effects; in fact, these agents have been shown to prevent birth abnormalities, as has been reviewed by Kennedy, 1993A-C and Kennedy, 1994. No toxicity due to BBIC has been reported in any human trial in which BBIC has been used. Nevertheless, although deleterious effects were not expected from the use of dietary BBI/BBIC, early human clinical trials with BBIC are limited to post-menopausal females so that potential problems for a developing embryo can not occur.
In a dose-ranging trial of BBIC in humans with benign prostatic hyperplasia for a 6 month period, there were found to be no increased adverse symptoms or abnormalities in standard laboratory assays when compared to placebo administration for the same time period (Malkowicz, et al., The Prostate 48:16-28, (2001); see also following Tables 1 and 2 listing toxicity study findings). The highest BBIC dose given was 400 CI units twice daily, which is the same as that of the present invention. Accordingly, no toxicity issues are expected in the treatment of humans with BBIC for MS or other inflammatory autoimmune diseases.
TABLE 1 Toxicities: in Treated Patients Maximum Toxicity Score Outcome N 0 1 2 3 4 WBC 14 12 (86%) 2 (14%) 0 0 0 Hemogloblin 14 12 (86%) 2 (14%) 0 0 0 Hematocrit 14 13 (93%) 1 (7%) 0 0 0 Platelet 14 13 (79%) 1 (7%) 0 0 0 Granulocytes a 7 6 (86%), 1 (14%) 0 0 0 Lynphocytes 14 9 (64%) 5 (36%) 0 0 0 Mononuclear Cells ab 6 4 (67%) 2 (33%) 0 0 0 Eosinophils 14 13 (93%) 1 (7%) 0 0 0 Basophils 14 13 (93%) 1 (7%) 0 0 0 Calcium 14 14 (100%) 0 0 0 0 Lipase 14 11 (79%) 2 (14%) 1 (7%) 0 0 Amylase 14 12 (86%) 1 (7%) 1 (7%) 0 0 Sodium 14 10 (71%) 4 (29%) 0 0 0 Potassium 14 12 (86%) 2 (14%) 0 0 0 Chloride 14 11 (79%) 3 (21%) 0 0 0 Carbon Dioxide 14 11 (79%) 3 (21%) 0 0 0 Urea/Nitrogen 14 11 (79%) 3 (21%) 0 0 0 Creatinine 14 12 (86%) 2 (14%) 0 0 0 Total Bilirubin 14 13 (93%) 1 (7%) 0 0 0 ALT 14 10 (710/,) 4 (29%) 0 0 0 AST 14 14 (100%) 0 0 0 0 Alkaline Phosphatase 14 14 (100%) 0 0 0 0 a - These measurements were not taken for Arizona patients. b - One patient had mononuclear cell measurements at baseline only. TABLE 2 Toxicities in Control Patients (N = 4) Maximum Toxicity Score Outcome 0 1 2 3 4 WBC 4 0 0 0 0 Hemoglobin 4 0 0 0 0 Hematocrit 4 0 0 0 0 Platelet 3 1 0 0 0 Granulocytes a 2 0 0 0 0 Lynphocytes 2 2 0 0 0 Mononuclear Cells ab 2 0 0 0 0 Eosinophils 4 0 0 0 0 Basophils 4 0 0 0 0 Calcium 4 0 0 0 0 Lipase 4 0 0 0 0 Amylase 3 1 0 0 0 Sodium 4 0 0 0 0 Potassium 3 1 0 0 0 Chloride 3 1 0 0 0 Carbon Dioxide 2 2 0 0 0 Urea/Nitrogen 3 1 0 0 0 Creatinine 3 1 0 0 0 Total Bilirubin 4 0 0 0 0 ALT 2 2 0 0 0 AST 4 0 0 0 0 Alkaline Phosphatase 4 0 0 0 0 a - These measurements were not taken for Arizona Patients.
a - These measurements were not taken for Arizona Patients.
Administration of an effective amount of the claimed compositions, either as a prophylactic dietary supplement or a pharmaceutical, is within the teachings of the invention. The term "effective amount" refers to an amount which alters the expression of certain types of proteolytic activities. Such an amount can be determined by those of skill in the art in accordance with known methods. For example, based on information determined in the accompanying Example, the preferred dose is 300-3000 mg/day, more preferably 400-1000 mg/day, most preferably about 800 mg/day. However, doses in the range of 200-4000 mg/day are effective in humans (50-100 .mu.g/mlx4000 ml (average blood volume in man)=200-400 mg BBIC; (100-400 CI units of BBIC is equivalent to 1000-4000 mg BBIC, as described in Kennedy, Prevent. Med. 22:796-811, pp. 797 (1993D)). Optimal dosage may vary by body weight.
Further, based on data from the published literature, doses of purified BBI as low as 1.3 mg/day (in rats) and more than 150 mg/day are effective in animal models of carcinogenesis (St. Clair et al., Cancer Res. 50:580-586 (1990); Kennedy, 1995C; van Hofe et al., Carcinogenesis 12:2147-2150 (1991)). Doses lower than 1 mg/day to rats are likely to be effective as well (Kennedy, J. Cell. Biochem. 22:188-194 (1995D)), with doses of as little as 0.001.mu.g/ml showing activity in vitro to suppress the malignant transformation of irradiated cells (Yavelow et al., 1985). Such in vitro results would suggest that doses considerably lower than human doses of 2000 mg (2000 mg BBIC=200 CI units) BBIC per day might be effective in the treatment of inflammation.
Compositions of the present invention may be administered parenterally, rectally, topically, transdermally or orally. However, the preferred administration is oral. Administration as either a prophylactic dietary supplement or as a pharmaceutical are contemplated. Published studies have shown that BBI is effective following a variety of routes of administration, including oral dosing (Kennedy, 1995C; Evans et al., Radiat. Res. 132:259-262 (1992)). Examples of pharmaceutical or prophylactic dietary supplement formulations include, but are not limited to, syrups, suspensions, emulsions, tablets, capsules, lozenges and mouthwashes.
One embodiment of the invention is a liquid formulation comprising a suspension or solution of the composition in a pharmaceutically acceptable liquid carrier. Suitable liquid carriers include, but are not limited to, ethanol, glycerin, non-aqueous solvents such as polyethylene glycols, oils or water with a suspending agent, preservatives, flavorings or coloring agents, or any suitable combination thereof.
In another embodiment, a composition in the form of a tablet is prepared using any suitable pharmaceutical carrier routinely used for preparing solid formulations. Examples of such carriers include, but are not limited to, magnesium stearate, starch, lactose, sucrose and cellulose. Pharmaceutically acceptable fillers and supplements may also be added.
Compositions in the form of capsules are prepared using routine encapsulating procedure. For example, pellets, granules or powder containing a composition of the instant invention can be prepared using standard carriers and then filled into a hard gelatin capsule. Alternately, a dispersion or suspension can be prepared using any suitable pharmaceutical carrier(s), and the dispersion or suspension is then filled into a soft gelatin capsule. Suitable pharmaceutical carriers include, but are not limited to, aqueous gums, cellulose, silicates and oils.
In yet another embodiment, a composition for parenteral administration is formulated as a solution or suspension. This solution or suspension will generally include the composition of the instant invention in a sterile aqueous carrier or parenterally acceptable oil. Examples of parenterally acceptable oils include, but are not limited to, polyethylene glycol, polyvinyl pyrrolidone, lecithin, arachis oils and sesame oil. Alternatively, the solution can be lyophilized and then reconstituted with a suitable solvent just prior to administration.
In addition, the BBI/BBIC composition is administered to the patient in conjunction with other drugs, medicaments, treatments or therapies to achieve reduction, suppression, inhibition or elimination of inflammation in the patient suffering from an inflammatory autoimmune disease, particularly a neuroinflammatory disease.
Claim 1 of 12 Claims
What is claimed is:
1. A method for treating chronic neuroinflammation in a patient with neuroinflammatory autoimmune disease comprising administering to the patient an amount of Bowman Birk Inhibitor effective to reduce, inhibit, or suppress the chronic inflammation.