Pulsatile GnRH Administration for Food Intake Control
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Solution Overview
Problem
Current treatments for obesity and anorexia-related disorders are inadequate due to adverse effects and inefficacies of existing medications, and there is a need for safer and more effective methods to control food intake behavior.
Innovation Solution
Pulsatile administration of gonadotropin-releasing hormone (GnRH) and microRNA compounds such as miR-200 and miR-155 to regulate food intake by restoring normal GnRH/LH pulsatile patterns, which are altered in obesity and anorexia, thereby addressing metabolic and reproductive axis dysfunctions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional obesity medications (phenylpropanolamine, dexfenfluramine, phentermine/fenfluramine, sibutramine, orlistat) are used to treat obesity, then food intake is reduced, but serious adverse effects occur including valvular heart disease toxicity
Solution Approach 1:
The patent changes the physiological parameter of GnRH secretion pattern from continuous or irregular to pulsatile administration, which naturally regulates food intake without the harmful side effects of conventional medications. The pulsatile pattern mimics the body's natural hormonal rhythm, achieving effective appetite control through physiological synchronization rather than pharmacological suppression.
Solution Approach 2:
The patent employs the body's own GnRH system to regulate food intake, allowing the endogenous hormonal pathway to control appetite and metabolism. This self-regulating mechanism eliminates the need for external medications with harmful side effects, as the body's natural pulsatile GnRH secretion pattern is harnessed to achieve therapeutic effects.
2Productivity
If GnRH is administered continuously to treat food intake disorders, then food intake control is achieved, but the natural pulsatile pattern is disrupted and reproductive function is impaired
Solution Approach 1:
The patent implements periodic pulsatile administration of GnRH that precisely replicates the natural secretion pattern. By using pulse intervals, amplitudes, and frequencies that match endogenous GnRH rhythms, the treatment achieves food intake control while preserving the pulsatile signal necessary for normal reproductive function and HPG axis operation.
Solution Approach 2:
The patent employs dynamic adjustment of GnRH pulse parameters (timing, duration, amplitude) to match the individual's natural pulsatile pattern. This dynamic approach allows the system to adapt to varying physiological states while maintaining both food intake control and reproductive functionality through synchronized hormonal rhythm.
3Productivity
If GnRH pulsatile administration is used to treat obesity, then food intake is normalized and metabolic impairments are reversed, but the treatment protocol becomes more complex
Solution Approach 1:
The patent replaces complex mechanical or behavioral diet-control systems with a hormonal mechanism. By using pulsatile GnRH administration, the treatment leverages the body's natural endocrine system to regulate food intake, substituting elaborate external control mechanisms with a simpler physiological pathway that achieves the same therapeutic goal.
Solution Approach 2:
The patent utilizes GnRH, a hormone already essential for reproductive function, to simultaneously achieve food intake control and metabolic regulation. This multi-functional approach allows a single pulsatile administration protocol to address both reproductive health and obesity treatment, reducing the need for separate specialized interventions.
Data Source
AI summary
The present invention relates to the pulsatile administration of the gonadotropin-releasing hormone (GnRH) for the treatment of food intake related disorder related disorder such as obesity (overeating) and anorexia (undereating). The inventors demonstrated that a population of mutant mice expressing BoNT/B in GnRH neurons (Gnrh::cre;iBot overweight), in which the GnRH release is inhibited, did not only fail to reach puberty onset and showed hypogonadotropic hypogonadism, but also developed overweight and hyperleptinemia. Unexpectedly, they found that the increase in body weight in mutant mice persisted in adulthood despite a significant decrease in food intake. Using a mouse model of obesity inventors observed an altered pattern of pulsatile LH secretion and that the frequency of LH pulses is inversely correlated to body weight and adiposity demonstrating that the heavier the animals were getting the more the GnRH/LH pulsatile pattern was altered. The present inventors further demonstrated that pulsatile GnRH treatment can allow to restore a control/lean pattern of GnRH/LH release in obese mice, and that this pulsatile administration of a “lean pattern” of native GnRH peptide in obese mice normalized their cumulative food intake to levels comparable with lean mice.