Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Hormone or other secreted growth regulatory factor,...
Reexamination Certificate
1998-08-11
2001-10-16
Bansal, Geetha P. (Department: 1642)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Hormone or other secreted growth regulatory factor,...
C424S094100, C514S008100, C514S021800
Reexamination Certificate
active
06303127
ABSTRACT:
FIELD OF INVENTION
This invention relates generally to methods and materials for the treatment and amelioration of the symptoms associated with cardiomyopathy in non-human animals, Parkinson's Disease, and degenerative liver disease including cirrhosis.
BACKGROUND OF THE INVENTION
Cardiomyopathy is a disease of the heart muscle. This form of heart disease is often distinctive, both in general symptoms and in patterns of blood flow, to allow a diagnosis to be made. Increasing recognition of this disease, along with improved diagnostic techniques, has shown that cardiomyopathy is a major cause of morbidity and mortality. In some areas of the world it may account for as many as 30 percent of all deaths due to heart disease.
Cardiomyopathy can result from a variety of structural or functional abnormalities of the ventricular myocardium. A large number of cardiomyopathies are apparently not related to an infectious process and are not well understood. Some are congenital and may cause enlargement of the heart. Metabolic diseases associated with endocrine disorders may also cause cardiomyopathies. Infections, such as acute rheumatic fever and several viral infections, may cause a number of types of myocarditis. Myocarditis may also occur as a manifestation of a generalized hypersensitivity reaction, allergic or immunologic. The heart may also be affected by any of a considerable number of collagen diseases. Collagen is the principal connective tissue protein, and collagen diseases are diseases of the connective tissues. They include diseases primarily of the joints, skin, and systemic disease.
There are three clinical classifications of cardiomyopathy; hypertrophic, restrictive, and dilated congestive. Dilated congestive cardiomyopathy is a disorder of myocardial function where ventricular dilation occurs, often following virus infection. Restrictive cardiomyopathy occurs as a consequence of the ventricular walls becoming rigid so that the chambers are unable to fill adequately. This is usually idiopathic. Hypertrophic cardiomyopathy is characterized by ventricular hypertrophy and may be congenital or acquired. The prognosis for all three types of disease is guarded at best and often poor. Treatment of cardiomyopathy involves restricted activity, stress avoidance, treatment with beta-blockers, prophylactic antibiotic therapy, use of anti-coagulants, calcium channel blockers, surgery, and cardiac transplantation.
Of interest to the present application are the disclosure of co-owned published PCT international applications PCT/US91/01898 published Nov. 14, 1991, PCT/US95/06689 published Nov. 30, 1995, and PCT/US97/14005 filed Aug. 8, 1997 and U.S. Pat. No. 5,753,624 issued May 19, 1998 the disclosures of which are hereby incorporated by reference. These references relate in part to methods for alleviating symptoms associated with amyloid plaque formation and/or formation of arterial plaques comprising the step of administering to a patient an effective amount of amyloid protein.
Recent literature reports have focused on the use of somatotropin, a growth hormone, for the treatment of cardiomyopathy. See: “A Preliminary Study of Growth Hormone in the Treatment of Dilated Cardiomyopathy, ”
N.E. J. of Medicine,
334(13), pp. 811-814 (1996). However, cautionary responses to such reports speak to the possibility, or even likelihood, of inducing cancer, arrhythmias, and other problems with growth hormone therapy using the concentrations now being evaluated by those authors. Accordingly, there remains a desire in the art for effective cardiomyopathy therapies that allow reduction in the amount of growth hormone administered and do not suffer from the limitations of the prior methods.
SUMMARY OF THE INVENTION
The present invention relates to the discovery that treatment of cardiomyopathy with a combination of compounds is effective in improving heart function. The therapeutic composition described herein is comprised of three compounds, each with a specific function relative to the amelioration of symptoms associated with cardiomyopathy. They are: beta-amyloid protein, streptolysin O, and growth hormone. It has been found that the administration of these compounds in combination is surprisingly effective in treating the symptoms associated with cardiomyopathy and allows a reduction in the amount of growth hormone required for a useful therapeutic effect.
Beta-amyloid acts to reduce vascular plaquing that may be associated with the disease. Streptolysin O reduces or eliminates cardiac scarring associated with the heart disease. Streptolysin O is one of a group of filterable hemolysins derived from Group A beta-hemolytic streptococci. Specifically, streptolysin O is a 60kD peptide which is hemolytic in its reduced state but is inactivated upon oxidation. Streptolysin O is used in the art generally as an analytical reagent for permeabilizing cells. See, e.g., Razin et al.,
Proc. Nat'l. Acad. Sci. (USA),
91:7722-7726 (1994). Co-owned U.S. Pat. No. 5,576,289, the disclosure of which is incorporated by reference, discloses the use of streptolysin O in methods for treating disease states characterized by motor deficit disorders. No disclosure is made in that patent of utility of streptolysin O in treating cardiomyopathy.
Growth hormone stimulates healing of the compromised heart. Growth hormone functions to regulate somatic growth and also maintains muscle mass and strength. It can also act as a counterregulatory hormone opposing the action of insulin on carbohydrate and lipid metabolism.
It has been discovered that by administration of a combination of the above compounds symptoms associated with cardiomyopathy are reduced or stabilized. The present invention provides methods for treating cardiomyopathy by administration of an effective amount of a composition comprising beta-amyloid, streptolysin O, and growth hormone. Methods of the invention result in amelioration of the symptoms associated with cardiomyopathy such as angina, fatigue, loss of strength, respiratory insufficiency, edema, interrupted sleep, recurrent respiratory infection, and the like. Noticeable improvement and/or stabilization of the disease symptoms were obtained after treatment. Improved Ejection Fraction (EF), blood pressure, and echo cardiogram readings were also noted in some cases.
The invention comprises the step of administering an effective amount of beta-amyloid, streptolysin O, and growth hormone in combination, to a human or non-human subject suffering from cardiomyopathy. The precise dose will vary among patients and may readily be determined by those skilled in the art. Useful dosages generally range from about 1×10
−11
mg to 10 mg of beta-amyloid, about 0.0005 units to 50 units streptolysin O, and about 1×10
−16
I.U. to 100 I.U. growth hormone, with preferred dosages of from about 10
−7
mg to 1.0 mg, 0.1 units to 10 units, and 10
−4
I.U. to 10 I.U., of each compound respectively. It is particularly preferred that dosages of about 0.1 I.U. or less of growth hormone be used to minimize potential negative effects of growth hormone therapy. Most preferred is the use of growth hormone at dosages of 0.01 I.U. or less. The compositions of the invention may be administered by a variety of routes of administration including intravenous, intramuscular, subcutaneous, intrathecal, and oral, with sublingual administration being preferred. It is also anticipated that alternative routes of administration may be by inhalation and topical application.
The preferred dosage for sublingual application is 1-10 drops (0.05 ml/drop) per day according to the above formula. Subcutaneous injections are administered 1-3 times a day.
The invention further provides Parkinson's Disease in a subject, comprising the step of administering to a subject diagnosed with Parkinson's Disease a composition comprising an effective amount of beta-amyloid, streptolysin O, and growth hormone. The precise dose will vary among patients and may readily be determined by those skilled in the art. Usef
Gurney Harry C.
McMichael John
Bansal Geetha P.
Marshall Gerstein & Borun
Milkhaus Laboratory, Inc.
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