US2011301103A1PendingUtilityA1
Methods of Treatment
Individually held — no corporate assignee on recordPriority: Jun 5, 2010Filed: Jun 2, 2011Published: Dec 8, 2011
Est. expiryJun 5, 2030(~3.9 yrs left)· nominal 20-yr term from priority
Inventors:Sumant S Chugh
A61P 3/10A61P 7/00A61P 3/06A61P 43/00A61P 7/10A61P 3/00A61P 13/02A61P 13/12C07K 14/00C07K 14/435G01N 2800/042A61K 31/7012G01N 2800/56G01N 2800/52A61K 31/7008G01N 2800/347
45
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Claims
Abstract
The present disclosure provides a biochemical basis of nephrotic syndrome and provides and explanation for the observed proteinuria and other effects. As a result, the present disclosure provides method for treating and/or preventing nephrotic syndrome as well as methods of alleviating symptoms associated with nephrotic syndrome. The present disclosure further provides methods for reducing proteinuria in nephrotic syndrome and other disease states as discussed herein.
Claims
exact text as granted — not AI-modified1 . A method for the treatment or prevention of a diabetic condition in a subject, said method comprising the step of administering a sialic acid, a sialic acid precursor or a combination of the foregoing to the subject.
2 . The method of claim 2 , wherein the diabetic condition is diabetic nephropathy, diabetes mellitus, lupus nephritis or primary glomular disease.
3 . The method of claim 1 , wherein the sialic acid precursor has the structure
wherein:
A is CH 2 or NH;
B, C, D and E are each independently selected from the group consisting of: H, OH, X, O—CO—X or O—X, wherein X is a substituted or unsubstituted alkyl or alkenyl, X being selected independently for each group B, C and D;
G is H, OH, Y or O—Y, wherein Y is a substituted or unsubstituted alkyl or alkenyl.
4 . The method of claim 1 , wherein the sialic acid precursor has the structure
5 . The method of claim 3 , wherein X and Y are each independently a C1 to C5 alkyl.
6 . The method of claim 3 , wherein the sialic acid precursor is Bu4ManNAc, 3,4,6-O-Bu3ManNAc, 1,3,4-O-Bu3ManNAc N-levulinoyl sialic acid or N-levulinoylmannosamine.
7 . The method of claim 1 , wherein the sialic acid compound is administered in a therapeutically effective amount.
8 . The method of claim 1 , wherein the administration restores sialylation of a polypeptide involved in the etiology of nephrotic syndrome.
9 . The methods of claim 8 , wherein the polypeptide is Angptl4.
10 . A method for the treatment or prevention of nephrotic syndrome in a subject, said method comprising the step of administering a sialic acid, a sialic acid precursor or a combination of the foregoing to the subject.
11 . The method of claim 10 , wherein the nephrotic syndrome is characterized as minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy/membranous glomerulonephritis, membranoproliferative glomerulonephritis or diabetic nephropathy.
12 . The method of claim 10 , wherein the sialic acid precursor has the structure
wherein:
A is CH 2 or NH;
B, C, D and E are each independently selected from the group consisting of: H, OH, X, O—CO—X or O—X, wherein X is a substituted or unsubstituted alkyl or alkenyl, X being selected independently for each group B, C and D;
G is H, OH, Y, or O—Y wherein Y is a substituted or unsubstituted alkyl or alkenyl.
13 . The method of claim 10 , wherein the sialic acid precursor has the structure
14 . The methods of claim 12 , wherein X and Y are each independently a C1 to C5 alkyl.
15 . The method of claim 12 , wherein the sialic acid precursor is Bu4ManNAc, 3,4,6-O-Bu3ManNAc, 1,3,4-O-Bu3ManNAc N-levulinoyl sialic acid or N-levulinoylmannosamine.
16 . The method of claim 10 , wherein the sialic acid compound is administered in a therapeutically effective amount.
17 . The method of claim 10 , wherein the administering reduces edema, reduces proteinuria, increases plamsa albumin levels, reduces hypercholesterolemia, reduces hypertriglyceridemia or a combination of the foregoing.
18 . The method of claim 10 , wherein the administration restores sialylation of a polypeptide involved in the etiology of nephrotic syndrome.
19 . The methods of claim 18 , wherein the polypeptide is Angptl4.
20 . A method for determining the status of a subject with respect to nephrotic syndrome or a diabetic condition, said method comprising the steps of determining the level of sialylation of a polypeptide associated with nephrotic syndrome or the diabetic condition in the subject, comparing such level of sialylation to the level of sialylation in a control and determining that the subject is suffering from or at risk for nephrotic syndrome or the diabetic condition if the level of sialylation in the subject is less than the level of sialylation in the control.
21 . The method of claim 24 , wherein the polypeptide is Angptl4.
22 . A method for determining the efficacy of a treatment in a subject undergoing treatment for nephrotic syndrome or a diabetic condition, said method comprising the steps of determining the level of sialylation of a polypeptide associated with nephrotic syndrome or the diabetic condition in the subject, comparing such level of sialylation to the level of sialylation in a control or the level of sialylation in the subject prior to initiating treatment, and determining that the treatment is efficacious if the level of sialylation in the subject is equal to or approaching the level of sialylation in the control or if the level of sialylation in the subject is increased as compared to the level of sialylation in the subject determined prior to initiating treatment.
23 . The method of claim 26 wherein the polypeptide is Angptl4.Join the waitlist — get patent alerts
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