Use of Follistatin-Like Related Gene (FLRG) to Increase Muscle Mass

A method of increasing the growth of muscle tissue in a subject comprising administering to the subject a therapeutically effective amount of an inhibitor of myostatin expression or activity in combination with a therapeutically effective amount of FLRG either prior to, simultaneously with or following the inhibitor of myostatin expression or activity, thereby increasing muscle tissue growth in the subject.

A method of ameliorating the severity of a pathologic condition characterized, at least in part, by a decreased amount, development or metabolic activity of muscle comprising:

• (a) contacting a muscle cell of a subject in need thereof with an FLRG polynucleotide or polypeptide, and
• (b) comparing an increase in muscle tissue growth in the subject to muscle tissue growth of a corresponding subject treated with a specific inhibitor of myostatin expression or activity,
• wherein the increase in muscle tissue growth following administration of FLRG is greater as compared to the muscle tissue growth in the subject treated with an inhibitor of myostatin expression or activity, which is indicative of increasing the growth of muscle tissue in the subject as a result of FLRG administration, thereby ameliorating the severity of the pathologic condition.

A method of ameliorating the severity of a pathologic condition characterized, at least in part, by a decreased amount, development or metabolic activity of muscle in a subject comprising contacting a muscle cell of a subject in need thereof with an inhibitor of myostatin expression or activity in combination with FLRG either prior to, simultaneous with or following the inhibitor of myostatin expression or activity.

A transgenic non-human mammal whose genome contains a nucleic acid sequence comprising FLRG and a regulatory element comprising a muscle-specific promoter operably linked and integrated into the genome of the mammal, wherein the nucleic acid sequence is expressed so as to result in elevated levels of FLRG and an increase in muscle mass in the mammal as compared to a corresponding mammal whose genome contains a myostatin-null mutation or a decreased level of myostatin as compared with normal basal levels.

A transgenic non-human mammal whose genome contains a myostatin-null mutation or a decreased level of myostatin as compared with normal basal levels, a nucleic acid sequence comprising FLRG, and a regulatory element comprising a muscle-specific promoter operably linked and integrated into the genome of the mammal, wherein the nucleic acid sequence is expressed so as to result in elevated levels of FLRG and an increase in muscle mass in the mammal as compared to a corresponding mammal whose genome contains a myostatin-null mutation or a decreased level of myostatin alone.