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Growth differentiation factor receptors, agonists and antagonists thereof, and methods of using same

A growth differentiation factor and receptor technology, applied in the field of GDF-8 receptor, regulating myostatin signal transduction in cells, and affecting the composition of myostatin signal transduction, can solve the problem of reducing food absorption The amount, the lean protein has not been achieved, the process is slow, etc.

Inactive Publication Date: 2003-10-15
THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, progress in using leptin to treat obesity has been slow, and so far leptin has not lived up to initial expectations
[0008] Treatment of morbid obesity is currently limited to surgical removal of part of the small intestine, thereby reducing the amount of food (and calories) absorbed

Method used

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  • Growth differentiation factor receptors, agonists and antagonists thereof, and methods of using same
  • Growth differentiation factor receptors, agonists and antagonists thereof, and methods of using same
  • Growth differentiation factor receptors, agonists and antagonists thereof, and methods of using same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0246] Myostatin acts in a dose-dependent manner

[0247] This example demonstrates that the activity of myostatin to inhibit muscle growth is dependent on the level of myostatin expression in vivo.

[0248] Myostatin is a negative regulator of skeletal muscle mass (McPherron et al., supra, 1997; McPherron and Lee, supra, 1997). Myostatin knockout mice, which are homozygous for the deletion of the myostatin gene, have a 25-30% increase in total body weight. Examination of homozygous knockout mice revealed that the increase in muscle mass was due to an approximately 100-200% increase in total body skeletal muscle.

[0249] Mice heterozygous for the myostatin mutation also had increased total body weight. However, the increase in heterozygotes was smaller than that in homozygotes, and only one age and sex group was statistically significant in many assays. To determine whether heterozygous mice had an intermediate phenotype between wild-type and homozygous mice, the analysi...

Embodiment 2

[0252] The effects of myostatin decline with age in knockout mice

[0253] This example demonstrates that the difference in body weight between wild-type mice and homozygous myostatin knockout mice is reduced along with a decrease in muscle weight in the mutant mice.

[0254] Myostatin knockout mice are approximately 25-30% heavier than wild type mice at 5 months of age (McPherron et al., supra, 1997). However, this difference in total body weight was significantly smaller or disappeared completely as the animals got older. To determine whether this effect was due to the relative loss of body weight in the knockout mice, because of, for example, muscle decline, or because the wild-type mice gained relatively greater body weight, muscle weight was analyzed in detail as a function of age.

[0255] At all ages examined from 2 months to 17 months, mice homozygous for the mutant had significantly higher breast muscle weight than their wild-type littermates. The most dramatic di...

Embodiment 3

[0257] Myostatin affects fat accumulation in a dose-dependent manner

[0258] This example demonstrates that myostatin knockout mice are unable to accumulate fat and that the reduction in fat accumulation correlates with the level of myostatin expression in vivo.

[0259] As shown in Example 2, wild-type and mutant mouse fat The amount of accumulation. Fat pads in the inguinal, epididymis, and retroperitoneum of male mice were examined. At 2 months of age, the weight of any of these fat pads did not differ between wild-type and mutant mice. By 5 to 6 months of age, both wild-type and heterozygous knockout mice had a wide range of fat pad weights, with an average, approximately 3- to 5-fold increase in fat pad weight by the time the animals reached 9- to 10-month-old. Due to the wide range of fat pad weights observed in these animals, some animals showed greater increases (up to 10-fold) than others.

[0260] In contrast to wild-type and heterozygous knockout mice, fat pa...

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Abstract

The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including GDF-8 (myostatin) receptor, and functional peptide portions thereof. Additionally, the present invention provides a virtual representation of the GDF receptor or a functional peptide portion thereof. The present invention also provides a method for modulating the cellular effects of myostatin by contacting the cells with a drug that affects myostatin signal transduction in the cells. In addition, the present invention provides a method of ameliorating a serious pathological condition at least partially characterized by an abnormal Characterized by weight, development or metabolic activity. The invention also provides a method of modulating the growth of muscle or adipose tissue in a eukaryotic organism by administering to the organism an agent that affects myostatin signal transduction.

Description

technical field [0001] The present invention generally relates to growth differentiation factor (GDF) receptors, more particularly to GDF-8 (myostatin) receptors, and compositions that affect myostatin (myostatin) signal transduction in cells, and use These compositions modulate the method by which myostatin signals in cells. Background technique [0002] The amount of time, effort and expense each year spent by individuals who decide to lose weight in the United States is staggering. For many of these individuals, the goal is not just to look better, but more importantly to avoid some of the medical problems associated with being overweight. [0003] More than half of the adult population in the United States is considered overweight. Moreover, 20 to 30 percent of adult men and 30 to 40 percent of adult women in the United States are considered obese, with rates highest among the poor and minorities. The prevalence of obesity, defined as being at least about 20% above th...

Claims

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Application Information

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IPC IPC(8): G01N33/50A01K67/027A61K31/7088A61K38/22A61K39/395A61K45/00A61K48/00A61P1/14A61P3/00A61P3/04A61P3/10A61P21/00A61P25/02A61P43/00C07K14/71C07K14/715C07K16/28C07K16/42C12N1/15C12N1/19C12N1/21C12N5/10C12N15/09C12N15/85G01N33/15G01N33/53G01N33/566G01N33/74
CPCA01K67/0271A01K2227/105A01K2217/05C12N2830/85A01K2267/03A01K2217/00G01N2333/495G01N33/74A01K2217/075C07K14/71C12N15/8509A01K2267/0362A01K67/0276G01N2500/00C12N2830/008A01K2267/0306A01K2207/15A61P1/14A61P21/00A61P25/02A61P3/00A61P3/04A61P3/06A61P43/00A61P3/10
Inventor 李瑟瑾A·C·麦克弗伦
Owner THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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