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-10682393-B2
Publication Date
2020-06-16
Expiration Date
2032-05-04
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
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 and pharmaceutical compositions comprising one or more GDNF receptor agonists for regulating weight gain, metabolic syndrome, and insulin resistance. It discloses methods for treating or preventing obesity, metabolic syndrome, or insulin resistance by administering an effective amount of a GDNF receptor agonist to subjects in need thereof, including obese, overweight, or normal weight individuals. Administration routes may include oral, systemic, peripheral, and gene therapy methods among others.
The problem being solved addresses the increasing prevalence of obesity and its related complications such as cardiovascular disease, type 2 diabetes, and metabolic syndrome. Current treatment options like bariatric surgery and pharmaceuticals show limitations in long-term efficacy and side effects. There is a need for improved methods to regulate weight gain that also ameliorate associated metabolic dysfunctions. This disclosure identifies GDNF and its receptor agonists as agents capable of reducing weight gain and improving metabolic parameters by increasing energy expenditure, reducing adipogenesis, and enhancing insulin sensitivity.
Claims Coverage
The patent includes four independent claims focused on methods of treating steatohepatitis by administering specific GDNF polypeptides to humans in need.
Method of treating steatohepatitis with polypeptide SEQ ID NO: 7
A method comprising administering an effective amount of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 7 to a human subject diagnosed with or having steatohepatitis.
Method of treating steatohepatitis with polypeptide SEQ ID NO: 8
A method comprising administering an effective amount of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 8 to a human subject diagnosed with or having steatohepatitis.
Method of treating steatohepatitis with polypeptide SEQ ID NO: 9
A method comprising administering an effective amount of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 9 to a human subject diagnosed with or having steatohepatitis.
Method of treating steatohepatitis with polypeptide SEQ ID NO: 10
A method comprising administering an effective amount of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 10 to a human subject diagnosed with or having steatohepatitis.
The claims cover methods of treating steatohepatitis in humans using specific GDNF receptor agonist polypeptides defined by SEQ ID NOs:7-10, representing the main inventive features of this patent focusing on therapeutic application of these polypeptides.
Stated Advantages
GDNF over-expression results in resistance to high fat diet induced weight gain and reduction in visceral and renal fat.
Administration of GDNF improves insulin sensitivity and glucose tolerance despite high fat diet consumption.
GDNF reduces serum leptin, cholesterol, and triglyceride levels, improving lipid profiles.
The treatment results in increased basal metabolic rate and energy expenditure independent of food intake or activity levels.
GDNF suppresses adipogenesis and decreases expression of genes associated with lipogenesis and adipocyte differentiation.
GDNF treatment reduces hepatic steatosis and associated liver enzyme levels.
Documented Applications
Treatment or prevention of obesity, overweight, or excessive body fat conditions in mammals, including humans.
Regulation and treatment of metabolic syndrome and associated insulin resistance through administration of GDNF receptor agonists.
Treatment of insulin resistance and maintenance of normal fasting blood glucose levels.
Treatment of hepatic steatosis, including steatohepatitis, particularly in subjects diagnosed with fatty liver and excessive body fat.
Treatment or prevention of obesity-related diseases and conditions such as asthma, Blount's disease, cardiovascular disease, gallstones, hypertension, intracranial hypertension, osteoarthritis, Pickwickian syndrome, polycystic ovary syndrome, sleep apnea, type 2 diabetes, and other conditions associated with obesity and/or type 2 diabetes.
Interested in licensing this patent?