EP-4734992-A1 - METHODS AND COMPOSITIONS COMPRISING TRIGONELLINE FOR TREATING MUSCLE DECLINE AND A KIDNEY DYSFUNCTION

Abstract

The present disclosure generally relates to methods and compositions comprising trigonelline that treat or prevent a disease or condition associated with muscle decline and/or a kidney dysfunction. Moreover, methods and compositions comprising trigonelline for decelerate glomerular filtration rate (GFR) progression and/or decrease glomerular hyalinosis damage and/or to improve the lean mass of a muscle. In addition, methods and compositions comprising trigonelline to improve the lean mass of a muscle and/or to improve the muscle fiber size are disclosed. Also disclosed are methods and compositions comprising trigonelline to improve the level of at least one nicotinamide adenine dinucleotide. Also disclosed are methods and compositions comprising trigonelline to increase muscle stem cells and/or mitigate a decline of muscle stem cells.

Inventors

• KARAZ, Sonia
• FEIGE, Jerome
• SORRENTINO, VINCENZO

Assignees

• Société des Produits Nestlé S.A.

Dates

Publication Date

20260506

Application Date

20240627

Claims (20)

1. 1. A method of treating and/ or preventing a disease or condition associated with muscle decline and/or a kidney dysfunction, the method comprising administering to a subject in need thereof an effective amount of a composition comprising trigonelline or a trigonelline or a pharmaceutically acceptable salt thereof.
2. 2. The method of Claim 1, wherein the disease or condition is selected from chronic kidney disease, metabolic induced muscle wasting, end-stage renal disease, dialysis, diabetes, muscle loss and/or kidney failure due to hospitalization in the intensive care unit, Pompe disease, metabolic acidosis, methylmalonic aciduria, disuse atrophy, protein-energy wasting and combinations thereof.
3. 3. The method of Claim 1, wherein the muscle decline and/or the kidney dysfunction is treated and/ or prevented in an early stage of chronic kidney disease and/ or a late stage of chronic kidney disease.
4. 4. The method of Claim 1, wherein the muscle is tibialis anterior and/or extensor digitorum longus (EDL), and/or soleus muscle.
5. 5. The method of Claim 1, wherein the composition comprising trigonelline or trigonelline or a pharmaceutically acceptable salt thereof is administered enterally.
6. 6. The method of Claim 1, wherein the composition comprising trigonelline or trigonelline or a pharmaceutically acceptable salt thereof is administered parenterally.
7. 7. The method of Claim 1, wherein the composition comprising trigonelline or the trigonelline or a pharmaceutically acceptable salt thereof is administered in a composition selected from the group consisting of a food product, a food for special medical purposes (FSMP), a nutritional supplement, a dairy-based drink, a low-volume liquid supplement, a meal replacement beverage, and combinations thereof.
8. 8. The method of Claim 1, wherein the trigonelline is micronized.
9. 9. A method of achieving at least one result selected from the group consisting of (i)decelerating glomerular filtration rate (GFR) progression; (ii) decreasing glomerular hyalinosis damage in a subject in need thereof, the method comprising administering to the subject in need thereof an effective amount of a composition comprising trigonelline or a trigonelline or a pharmaceutically acceptable salt thereof.
10. 10. The method of Claim 9, wherein the subject has a disease or condition selected from chronic kidney disease, metabolic induced muscle wasting, end-stage renal disease, dialysis, diabetes, muscle loss and/or kidney failure due to hospitalization in the intensive care unit, Pompe disease, metabolic acidosis, methylmalonic aciduria, disuse atrophy, protein-energy wasting and combinations thereof.
11. 11. The method of Claim 9, wherein the composition comprising trigonelline or trigonelline or a pharmaceutically acceptable salt thereof is administered enterally.
12. 12. The method of Claim 9, wherein the composition comprising trigonelline or trigonelline or a pharmaceutically acceptable salt thereof is administered parenterally.
13. 13. The method of Claim 9, wherein the composition comprising trigonelline or the trigonelline or a pharmaceutically acceptable salt thereof is administered in a composition selected from the group consisting of a food product, a food for special medical purposes (FSMP), a nutritional supplement, a dairy-based drink, a low-volume liquid supplement, a meal replacement beverage and combinations thereof.
14. 14. The method of Claim 9, wherein the trigonelline is micronized.
15. 15. A method of achieving at least one result selected from the group consisting of (i) improving the lean mass of a muscle; (ii) improving the muscle fiber size; (iii) improving the level of at least one nicotinamide adenine dinucleotide in a muscle in a subject in need thereof, the method comprising administering to the subject in need thereof an effective amount of a composition comprising trigonelline or a trigonelline or a pharmaceutically acceptable salt thereof.
16. 16. The method of Claim 15, wherein the subject has a disease or condition selected from chronic kidney disease, metabolic induced muscle wasting, end-stage renal disease, dialysis, diabetes, muscle loss and/or kidney failure due to hospitalization in the intensive care unit, Pompe disease, metabolic acidosis, methylmalonic aciduria, disuse atrophy, protein-energy wasting and combinations thereof.
17. 17. The method of Claim 15, wherein the lean mass of a muscle is improved in an early stage of chronic kidney disease and/or a late stage of chronic kidney disease.
18. 18. The method of Claim 15, wherein the muscle is tibialis anterior and/or extensor digitorum longus (EDL), and/or soleus muscle.
19. 19. The method of Claim 15, wherein muscle atrophy is reduced.
20. 20. The method of Claim 15, wherein the at least one nicotinamide adenine dinucleotide is nicotinamide adenine dinucleotide in its oxidized form (NAD+) or reduced form (NADH).

Description

METHODS AND COMPOSITIONS COMPRISING TRIGONELLINE FOR TREATING MUSCLE DECLINE AND A KIDNEY DYSFUNCTION [0001] This application claims priority to U.S. provisional patent application no. 63/523,960 filed June 29, 2023, the entire contents of which are incorporated by reference. [0002] The present disclosure generally relates to methods and compositions comprising trigonelline that treat or prevent a disease or condition associated with muscle decline and/or a kidney dysfunction. Moreover, methods and compositions comprising trigonelline for decelerate glomerular filtration rate (GFR) progression and/or decrease glomerular hyalinosis damage and/or to improve the lean mass of a muscle. In addition, methods and compositions comprising trigonelline to improve the lean mass of a muscle and/or to improve the muscle fiber size are disclosed. Also disclosed are methods and compositions comprising trigonelline to improve the level of at least one nicotinamide adenine dinucleotide. BACKGROUND [0003] The loss of muscle mass that occurs during muscle wasting may be characterized by muscle protein degradation due to catabolism. Muscle protein catabolism, whether caused by a high degree of protein degradation or a low degree of protein synthesis, leads to a decrease in muscle mass and to muscle wasting. [0004] Muscle decline in form of muscle wasting is associated with chronic, neurological, genetic or infectious pathologies, diseases, illnesses or conditions. In particular muscle decline is related to chronic kidney disease (CKD), end stage renal failure (ESRD), metabolic dysfunction-induced muscle wasting, dialysis, diabetes, muscle loss and/or kidney failure due to hospitalization in the intensive care unit, Pompe disease, metabolic acidosis, methylmalonic aciduria, disuse atrophy, protein-energy wasting amongst others. [0005] Muscle wasting is a common complication of CKD, characterized by the loss of muscle mass, strength and function, which significantly increases the risk of morbidity and mortality in this population. Numerous complications associated with declining renal function and lifestyle activate catabolic pathways and impair muscle regeneration, resulting in substantial protein wasting. [0006] CKD is a gradual and progressive loss of the ability of the kidneys to excrete wastes, concentrate urine, reabsorb proteins and amino acids, and conserve electrolytes. Unlike acute kidney failure with its abrupt but reversible of kidney function, the kidney functions in chronic kidney disease progress and deteriorate irreversibly towards end stage renal disease (ESRD). CKD arises from many heterogeneous disease pathways that alter the function and structure of the kidney irreversibly, over months or years. [0007] Diabetes and hypertension are the main causes of CKD in all high-income and middleincome countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests such as urinary dipstick or blood tests, or when symptoms become severe. The best available indicator of overall kidney function is the glomerular filtration rate (GFR). Disease and management are classified according to stages of disease severity, which are assessed from GFR and albuminuria, and clinical diagnosis (cause and pathology). Presence of proteinuria is associated with increased risk of progression of CKD. The diagnosis of CKD rests on establishing a chronic reduction in kidney function and structural kidney damage. [0008] CKD is diagnosed using a staging system that demonstrates the amount of kidney function available (stage 1 = normal kidney function) and patients often do not present symptoms in the early stages. Stage 5 of CKD is ESRD, which is a complete or near complete failure of the kidneys and usually occurs when kidney function is less than 10% of baseline. SUMMARY OF THE INVENTION [0009] In a first aspect, the present disclosure provides a method of treating and/or preventing a disease or condition associated with muscle decline and/or a kidney dysfunction. The method comprises administering to a subject in need thereof an effective amount of a composition comprising trigonelline or a trigonelline or a pharmaceutically acceptable salt thereof. In one embodiment the muscle decline and/ or the kidney dysfunction is treated and/ or prevented in an early stage of chronic kidney disease and/ or a late stage of chronic kidney disease. [ooio] In another aspect, the present disclosure provides a method for decelerating glomerular filtration rate (GFR) progression in a subject in need thereof. The method comprises administering to the subject in need thereof an effective amount of a composition comprising trigonelline or a trigon