EP-4740950-A1 - PROPHYLACTIC OR AMELIORATING AGENT FOR CACHEXIA

Abstract

The present invention provides a preventing or ameliorating agent for cachexia, comprising a phospholipid and/or a lysophospholipid as an active ingredient; and a method for screening for a substance for ameliorating cachexia. The preventing or ameliorating agent for cachexia according to the present invention is effective for not only cancer cachexia but also cachexia caused by diseases other than cancer, inhibits skeletal muscle mass loss, inhibits lipoatrophy, and inhibits the expression of proinflammatory cytokines.

Inventors

• TAKAKURA NOBUYUKI
• RAHMAWATI Fitriana Nur
• UCHIDA TOMONORI
• HOSHINA RYOSUKE

Assignees

• The University of Osaka
• Kewpie Corporation

Dates

Publication Date

20260513

Application Date

20240702

Claims (10)

1. A preventing or ameliorating agent for cachexia, comprising a phospholipid and/or a lysophospholipid as an active ingredient.
2. The preventing or ameliorating agent according to claim 1, wherein the phospholipid is a phosphatidylcholine or a phosphatidylserine.
3. The preventing or ameliorating agent according to claim 1, wherein the lysophospholipid is a lysophosphatidylcholine or a lysophosphatidylserine.
4. The preventing or ameliorating agent according to claim 1, wherein the agent is used for inhibiting skeletal muscle mass loss.
5. The preventing or ameliorating agent according to claim 1, wherein the agent is used for inhibiting lipoatrophy.
6. The preventing or ameliorating agent according to claim 1, wherein the agent is used for inhibiting expression of a proinflammatory cytokine.
7. The preventing or ameliorating agent according to claim 1, wherein the cachexia is induced by a disease, wherein the disease that induces the cachexia is a chronic disease associated with inflammation.
8. The preventing or ameliorating agent according to claim 7, wherein the chronic disease associated with inflammation is a disease selected from the group consisting of cancer, chronic heart failure, chronic obstructive lung disease, chronic renal failure, chronic liver diseases, chronic infections, sepsis, autoimmune diseases, and diabetes mellitus.
9. A method for screening for a substance for ameliorating cachexia, comprising selecting a test substance that promotes myotube formation as compared to that without addition of the test substance when culture is performed in an in vitro differentiation induction system of a stem cell or a progenitor cell into a skeletal muscle cell using a differentiation induction medium containing a culture supernatant of a cancer cell with addition of the test substance.
10. A method for screening for a substance for ameliorating cachexia, comprising selecting a test substance that promotes adipocyte differentiation as compared to that without addition of the test substance when culture is performed in an in vitro differentiation induction system of a stem cell or a progenitor cell into an adipocyte using a differentiation induction medium containing a culture supernatant of a cancer cell with addition of the test substance.

Description

TECHNICAL FIELD The present invention relates to a preventing or ameliorating agent for cachexia. BACKGROUND ART Cachexia is the term referring to wasting of the body due to malnutrition. The definition of cachexia was emerged in a consensus conference held by European and American experts in 2007 and is as follows: "cachexia, is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. The prominent clinical feature of cachexia is weight loss in adults or growth failure in children. Anorexia, inflammation, insulin resistance and increased muscle protein breakdown are frequently associated with cachexia. Cachexia is distinct from starvation, age-related loss of muscle mass, primary depression, malabsorption and hyperthyroidism and is associated with increased morbidity" (Non-Patent Literature 1). Cachexia is especially characterized by loss of skeletal muscle mass. Wasting of skeletal muscle has a huge impact on the quality of life and the vital prognosis of the patients, and such a condition has become known as sarcopenia. Once cachexia is developed, motor ability and other abilities are reduced, and the recovery ability of the body declines. As a result, many diseases may become refractory to treatments, and the patients may lose the opportunity to receive therapy. As well known, the transition to cachexia in cancer patients may have a huge impact on the prognosis of most of the patients by taking away the opportunity to receive cancer therapy using therapeutic cancer drugs, which usually have substantial influence or adverse side effects on normal tissue. Needless to say, cachexia is associated with not only cancer but also many chronic wasting diseases, including chronic heart failure, chronic obstructive lung disease, chronic renal failure, chronic liver diseases, chronic infection and sepsis (e.g., AIDS, etc.), autoimmune diseases such as rheumatism, and diabetes mellitus. If cachexia occurs in patients with these diseases, the patients may become refractory to treatments. Currently, locally or systemically enhanced expression of proinflammatory cytokines has been considered a key causative factor of cachexia (Non-Patent Literature 2). However, the whole picture of cachexia has not been clarified yet. The pathology of cachexia is believed to involve a complex interplay of various factors, including metabolic disorders due to persistent tissue inflammation causing tissue damage and the acceleration of catabolism, and the loss of energy intake by lack of appetite or other causes. The elucidation of the molecular mechanisms of cachexia at the basic medical level is required, and there is a need for the development of a therapeutic drug capable of inhibiting cachexia. Conventionally, anti-inflammatory drugs, appetite-improving drugs (ghrelin receptor agonists), or selective androgen receptor modifiers with anabolism-promoting action and other drugs are applied to patients with cachexia. However, the effects of these drugs are limited, and the emergence of a therapeutic drug that is expected to significantly ameliorate cachexia has been desired. CITATION LIST NON-PATENT LITERATURE Non-Patent Literature 1: Evans WJ et al.: Cachexia: a new definition. Clinical Nutrition 2008; 27: 793-799.Non-Patent Literature 2: Cederholm T et al.: ESPEN guidelines on definitions and terminology of clinical nutrition. Clinical Nutrition 2017; 36: 49-64. SUMMARY OF INVENTION TECHNICAL PROBLEM An object of the present invention is to provide a cachexia-preventing or ameliorating agent that is effective for not only cancer cachexia but also cachexia caused by diseases other than cancer. Another object of the present invention is to provide a screening method for a substance for ameliorating cachexia. SOLUTION TO PROBLEM The present invention was made to solve the above problems and includes the following. [1] A preventing or ameliorating agent for cachexia, comprising a phospholipid and/or a lysophospholipid as an active ingredient.[2] The preventing or ameliorating agent according to the above [1], wherein the phospholipid is a phosphatidylcholine or a phosphatidylserine.[3] The preventing or ameliorating agent according to the above [1], wherein the lysophospholipid is a lysophosphatidylcholine or a lysophosphatidylserine.[4] The preventing or ameliorating agent according to any one of the above [1] to [3], wherein the agent is used for inhibiting skeletal muscle mass loss.[5] The preventing or ameliorating agent according to any one of the above [1] to [3], wherein the agent is used for inhibiting lipoatrophy.[6] The preventing or ameliorating agent according to any one of the above [1] to [3], wherein the agent is used for inhibiting expression of a proinflammatory cytokine.[7] The preventing or ameliorating agent according to any one of the above [1] to [6], wherein the cachexia is induced by a disease, wherein the disease that induces the cachexia