N-acetyl mannosammine as a therapeutic agent
Inventors
Huizing, Marjan • Gahl, William A. • Manoli, Irini • Klootwijk, Enriko
Assignees
US Department of Health and Human Services
Publication Number
US-10953026-B2
Publication Date
2021-03-23
Expiration Date
2028-05-30
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Abstract
The invention relates to compositions and methods for treating kidney and muscle dysfunction that involves use of therapeutic amounts of N-acetyl mannosamine.
Core Innovation
The invention relates to compositions and methods for treating kidney and muscle dysfunction by administering therapeutic amounts of N-acetyl mannosamine (ManNAc) or its derivatives to increase sialic acid levels in mammals. The invention provides methods to treat diseases involving sialic acid deficiency, including hereditary inclusion body myopathy (HIBM), certain muscular atrophies, and kidney diseases characterized by proteinuria and hematuria resulting from hyposialylation.
The invention addresses the lack of available treatments for HIBM, a progressive autosomal recessive neuromuscular disorder marked by muscle weakness and atrophy, and the absence of methods to treat associated kidney dysfunctions related to glomerular basement membrane and podocyte membrane abnormalities. It was discovered that administering ManNAc increases sialylation of kidney podocalyxin, improves podocyte foot morphology, and restores glomerular basement membrane integrity, thereby treating kidney disorders.
Claims Coverage
The patent includes multiple independent claims covering therapeutic methods using N-acetyl mannosamine or derivatives for treating various conditions. The inventive features span administration specifics, disease targets, and methods of delivery.
Therapeutic method administering N-acetyl mannosamine or derivatives for disease treatment
A method comprising selecting a mammal with a condition or disease and administering an effective amount of N-acetyl mannosamine or a defined derivative (Formula I) to increase sialic acid levels and treat the condition or disease.
Treatment of muscular and metabolic diseases by administration of N-acetyl mannosamine
A method of treating muscular atrophy, muscular dystrophy, high blood pressure, or diabetes in a mammal by administering a therapeutically effective amount of N-acetyl mannosamine, typically about 0.1 g to about 50 g per day.
Method of reducing proteinuria by administration of N-acetyl mannosamine or derivatives
Administering an effective amount of N-acetyl mannosamine or a defined derivative (Formula I) to a mammal with proteinuria to reduce protein leakage into urine and improve kidney function.
Sustained release and topical administration of N-acetyl mannosamine or derivatives
Methods comprising sustained release formulations or topical administration of N-acetyl mannosamine or its derivatives for therapeutic applications.
Oral and microencapsulated administration of N-acetyl mannosamine
Methods featuring oral administration or microencapsulation of N-acetyl mannosamine for effective delivery and treatment.
Reduction of hematuria and proteinuria through administration of N-acetyl mannosamine
Methods wherein administration of N-acetyl mannosamine or its derivatives reduces the presence of blood and protein in urine in mammals with kidney disorders.
The claims cover methods employing N-acetyl mannosamine or its derivatives to treat muscle-related diseases, kidney disorders involving proteinuria and hematuria, specific dosing regimens, routes of administration including oral, topical, and sustained release, and reduction of symptoms related to sialic acid deficiency.
Stated Advantages
Increased production of sialic acid leading to improved kidney function and muscle condition.
Improved sialylation of podocalyxin and other tissue-specific glycoproteins.
Reduction in proteinuria and hematuria in kidney disorders.
Improved morphology of podocyte foot processes and glomerular basement membrane integrity.
Enhanced survival and decreased pathology in animal models of disease upon ManNAc administration.
Documented Applications
Treatment of hereditary inclusion body myopathy (HIBM) and related myopathies involving sialic acid deficiency.
Therapy for kidney diseases characterized by proteinuria and hematuria due to defective sialylation, including podocytopathies and glomerular basement membrane diseases such as Alport disease and thin membrane disease.
Use in humans for treatment of muscular atrophy, muscular dystrophy, high blood pressure, and diabetes.
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