Treating and preventing disease with tma and tmao lowering agents

Abstract

Provided herein are compositions, systems, and methods for treating a disease, such as kidney disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and / or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and / or TMAO sequestering agent.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present invention claims priority to U.S. Provisional Patent Application 62 / 056,168, filed Sep. 26, 2014, which is incorporated by reference in its entirety.FIELD OF THE INVENTION[0002]Provided herein are compositions, systems, and methods for treating a disease, such as kidney disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and / or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent, or vii) a TMA and / or TMAO sequestering agent.BACKGROUND[0003]Kidneys of the human body function to remove excess fluids as well as some ions. The...

AI Technical Summary

Benefits of technology

The patent text describes methods for treating and preventing kidney disease with various agents and procedures. These methods may include reducing symptoms in subjects with kidney disease, preventing the development of chronic kidney disease in healthy subjects with elevated levels of TMAO, and preserving kidney function in subjects with age-related decline in kidney function. The methods may involve inhibiting the production or activity of TMAO, gut microbiota transplantation, delivering specific agents to the kidneys, or using antibiotics, probiotics, antiplatelet agents, or sequestering agents. This patent aims to provide effective means for promoting renal health and preventing TMAO-induced impairment of renal function.

Problems solved by technology

In patients with chronic kidney disease, kidney function is severely compromised.

Heart disease is the leading cause of death for all people having CKD.

Fluid accumulates in ESRD patients because the kidneys can no longer effectively remove water and other fluids from the body.

The fluid accumulates first in the blood and then accumulates throughout the body, resulting in swelling of the extremities and other tissues as edema.

This accumulation of fluid causes increased stress on the heart, in turn causing significant increases in blood pressure or hypertension, which can lead to heart failure.

Although the population of patients afflicted with CKD grows each year, there is no cure.

Although effective at removing waste components from blood, dialysis treatments are administered intermittently and, therefore, do not emulate the continuous function of a natural kidney.

However, the extracorporeal processing of the body fluids increases the discomfort, inconvenience and the costs associated with treatment.

There is also an additional risk of infection, which mandates that the procedures be carried out under the supervision of trained medical personnel.

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