Mechanisms involved in muscle atrophy
1 Purpose
The loss of skeletal muscle mass (atrophy) is a dramatic health situation that significantly increases the risk of death and reduces the quality of life. Currently, there exists no pharmaceutical drug on the market to prevent or cure atrophied muscle. Recently we discovered a molecule (called Drug X) able to increase the size of muscle cell and prevent atrophy in different in vitro models. The main purpose of this project is to investigate whether Drug X can prevent/cure muscle atrophy in vivo.
2 Distress
Mice treated with dexamethasone will lose muscle mass (about 10%)
Mice treated with LLC will lose muscle mass (about 10%)
3 Expected benefit
Skeletal muscle atrophy is observed in many situations including aging, chronic diseases (cancer, obesity, chronic obstructive pulmonary disease, kidney disease) and immobilization (injury, hospitalization/bed-rest). Regarding aging, at least 20% of the EU population is currently over 65 years of age (i.e. ~90 million of individuals), and about one-third of the European population is affected by a chronic disease (i.e. ~150 million of inhabitants). Knowledge emerged from the present project will contribute developing novel pharmaceutical(s) to prevent and/or cure muscle atrophy.
4 Number of animals, and what kind
550 including non-transgenic and transgenic mice. This number will increase to 650. This number will increase to 698.
5 How to adhere to 3R
The use of animals is unavoidable since we want to study the in vivo effect of Drug X on muscle atrophy. For example, there are no in vitro models allowing the investigation of the different skeletal muscle fiber types (slow- and fast-twitch muscle fibers). We will use the minimum number of animals required for our analysis and we will monitor closely the well being of the animals.
The mice will be exposed to various methods that individually are categorized with none to moderate distress. There is therefore little room for improvements in the planned experimental procedures. Animal health will be monitored carefully. A score sheet will be used to identity mice that reaches the predefined humane endpoint, and such mice will be euthanized to minimize distress.
6 Modification
The inclusion of mdx mutant and non-mdx mutant mice will increase the human relevance of our research.
The inclusion of the cancer cachexia will increase the human relevance of our research.
The loss of skeletal muscle mass (atrophy) is a dramatic health situation that significantly increases the risk of death and reduces the quality of life. Currently, there exists no pharmaceutical drug on the market to prevent or cure atrophied muscle. Recently we discovered a molecule (called Drug X) able to increase the size of muscle cell and prevent atrophy in different in vitro models. The main purpose of this project is to investigate whether Drug X can prevent/cure muscle atrophy in vivo.
2 Distress
Mice treated with dexamethasone will lose muscle mass (about 10%)
Mice treated with LLC will lose muscle mass (about 10%)
3 Expected benefit
Skeletal muscle atrophy is observed in many situations including aging, chronic diseases (cancer, obesity, chronic obstructive pulmonary disease, kidney disease) and immobilization (injury, hospitalization/bed-rest). Regarding aging, at least 20% of the EU population is currently over 65 years of age (i.e. ~90 million of individuals), and about one-third of the European population is affected by a chronic disease (i.e. ~150 million of inhabitants). Knowledge emerged from the present project will contribute developing novel pharmaceutical(s) to prevent and/or cure muscle atrophy.
4 Number of animals, and what kind
550 including non-transgenic and transgenic mice. This number will increase to 650. This number will increase to 698.
5 How to adhere to 3R
The use of animals is unavoidable since we want to study the in vivo effect of Drug X on muscle atrophy. For example, there are no in vitro models allowing the investigation of the different skeletal muscle fiber types (slow- and fast-twitch muscle fibers). We will use the minimum number of animals required for our analysis and we will monitor closely the well being of the animals.
The mice will be exposed to various methods that individually are categorized with none to moderate distress. There is therefore little room for improvements in the planned experimental procedures. Animal health will be monitored carefully. A score sheet will be used to identity mice that reaches the predefined humane endpoint, and such mice will be euthanized to minimize distress.
6 Modification
The inclusion of mdx mutant and non-mdx mutant mice will increase the human relevance of our research.
The inclusion of the cancer cachexia will increase the human relevance of our research.