Methods of Treatment

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.

Description

STATEMENT AS TO FEDERALLY SPONSORED RESEARCH[0001]Funding for the work described herein was provided by the federal government, which has certain rights in the invention.FIELD OF THE DISCLOSURE[0002]The present disclosure is directed to methods for the treatment and prevention of nephrotic syndrome, diabetic conditions and conditions related thereto.BACKGROUND[0003]Nephrotic syndrome is caused by various disorders that damage the kidneys, particularly specialized cells called podocytes and the basement membrane of the glomerulus. Diabetic nephropathy and membranous glomerulonephritis (also called membranous nephropathy) are common causes in adults, whereas minimal change disease is the most common cause in children. Characteristics of nephrotic syndrome includes loss of protein in the urine (proteinuria), hyperlipidemia (hypercholesterolemia and hypertriglyceridemia), hypoalbuminemia (low blood albumin or protein levels) and edema. Proteinuria is defined as the presence of an excess...

AI Technical Summary

Benefits of technology

[0060]In a first aspect, the present disclosure provides methods of treatment and / or prevention of nephrotic syndrome in a subject. In one embodiment, the nephrotic syndrome is characterized as minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) / membranous glomerulonephritis (MGN) membranoproliferative glomerulonephritis (MPGN), and diabetic nephropathy. In another embodiment, the nephrotic syndrome is characterized as MCD. The methods comprise the step of administering to a subject sialic acid or a sialic acid precursor. The sialic acid or sialic acid precursor may be administered at a therapeutically effective dose, either alone, as a part of a pharmaceutical composition or in combination with a secondary agent. Such administration restores normal sialylation of a polypeptide, such as, but not limited to Angptl4, involved in the etiology of nephrotic syndrome, thereby treating or preventing nephrotic syndrome in the subject.

[0065]In a sixth aspect, the present disclosure provides methods of reducing hypercholesterolemia in a subject. In one embodiment, the subject is suffering from nephrotic syndrome. In one embodiment, the nephrotic syndrome is characterized as MCD, FSGS, MN / MGN, MPGN or diabetic nephropathy. In another embodiment, the nephrotic syndrome is characterized as MCD. In a specific embodiment, the hypercholesterolemia is caused, at least in part, by hyposialylation of a polypeptide, such as, but not limited to, Angptl4. The methods comprise the step of administering to a subject sialic acid or a sialic acid precursor. The sialic acid or sialic acid precursor may be administered at a therapeutically effective dose, either alone, as a part of a pharmaceutical composition or in combination with a secondary agent. Such administration restores normal sialylation of the polypeptide, such as, but not limited to Angptl4, involved in the induction of hypercholesterolemia thereby reducing hypercholesterolemia in the subject.

[0066]In a seventh aspect, the present disclosure provides methods of reducing hypertriglyceridemia in a subject. In one embodiment, the subject is suffering from nephrotic syndrome. In one embodiment, the nephrotic syndrome is characterized as MCD, FSGS, MN / MGN, MPGN or diabetic nephropathy. In another embodiment, the nephrotic syndrome is characterized as MCD. In a specific embodiment, the hypertriglyceridemia is caused by hyposialylation of a polypeptide, such as, but not limited to, Angptl4. The methods comprise the step of administering to a subject sialic acid or a sialic acid precursor. The sialic acid or sialic acid precursor may be administered at a therapeutically effective dose, either alone, as a part of a pharmaceutical composition or in combination with a secondary agent. Such administration restores normal sialylation of the polypeptide, such as, but not limited to Angptl4, involved in the induction of hypertriglyceridemia thereby reducing hypertriglyceridemia in the subject.

Problems solved by technology

When protein is lost in the urine, its blood concentration decreases, allowing water to move into other areas of the body, which leads to swelling known as edema.

Additionally, because of this extra fluid that stays in the body, people often gain weight, experience fatigue and may find that they urinate less often.

Therapy designed to reduce proteinuria further complicates the study of disease mechanisms.

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