Glial cell line derived neurotrophic factor, obesity, and obesity-related diseases and conditions
Inventors
Assignees
Emory University • US Department of Veterans Affairs
Publication Number
US-10052362-B2
Publication Date
2018-08-21
Expiration Date
2032-05-04
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Abstract
The disclosure relates to therapeutic methods for regulating weight gain, metabolic syndrome, and insulin resistance. In certain embodiments, the disclosure relates to methods of treating or preventing obesity, metabolic syndrome, or insulin resistance by administering an effective amount of a pharmaceutical composition comprising one or more GDNF receptor agonists to a subject in need thereof.
Core Innovation
The invention provides therapeutic methods for regulating weight gain, metabolic syndrome, and insulin resistance by administering an effective amount of pharmaceutical compositions comprising one or more GDNF receptor agonists. These methods treat or prevent obesity and related conditions by modulating energy expenditure and adipogenesis through the activation of GDNF signaling pathways.
The core problem addressed is the prevalence of obesity and its associated complications such as cardiovascular disease, type 2 diabetes, and metabolic syndrome. Existing treatments are limited by their efficacy and potential complications, creating a need for improved methods to regulate weight gain and metabolic dysfunction.
The invention demonstrates that over-expression or administration of GDNF or GDNF receptor agonists enhances energy expenditure, decreases adipogenesis, improves insulin sensitivity, and reduces hepatic steatosis. It outlines various administration routes and compositions, including recombinant GDNF, homologs, peptides, mutants, and small molecule mimetics, applicable to subjects with obesity, metabolic syndrome, or insulin resistance.
Claims Coverage
There are six independent claims focusing on methods of treating non-alcoholic fatty liver disease using specific GDNF polypeptides.
Use of specific GDNF polypeptides for treatment
Administering an effective amount of polypeptides comprising amino acid sequences SEQ ID NO: 7, 8, 9, or 10 to subjects diagnosed with fatty liver disease, particularly where body fat exceeds 20% of total body weight.
Application to human subjects
The methods specifically include treatment of human subjects diagnosed with fatty liver and excess body fat using the specified GDNF receptor agonists.
The claims cover methods of treating non-alcoholic fatty liver disease through administration of particular GDNF polypeptide sequences to humans, targeting subjects with diagnosed fatty liver and elevated body fat, thereby defining a therapeutic use of these agonists for liver disease associated with obesity.
Stated Advantages
GDNF administration results in resistance to high fat diet-induced weight gain and reduces visceral and renal fat.
GDNF improves glucose tolerance, lowers serum leptin, and increases adiponectin, indicating improved insulin sensitivity.
GDNF reduces hepatic steatosis even with a high fat diet.
GDNF increases basal metabolic rates and energy expenditure without increasing food consumption.
Potential for peripheral or systemic administration targeting adipose tissue due to expression of GDNF receptors in white adipose tissue.
Documented Applications
Treatment or prevention of obesity, overweight, and excessive body fat conditions.
Treatment of metabolic syndrome by administering GDNF receptor agonists.
Treatment of insulin resistance in subjects diagnosed or exhibiting symptoms thereof.
Treatment of non-alcoholic fatty liver disease and hepatic steatosis.
Treatment or prevention of diseases and conditions associated with obesity and type 2 diabetes including asthma, cardiovascular disease, gallstones, hypertension, osteoarthritis, polycystic ovary syndrome, sleep apnea, steatohepatitis, and type 2 diabetes.
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