Rhythm is dedicated to understanding rare genetic diseases of obesity caused by an impaired pathway in the brain known as the melanocortin-4 receptor (MC4R) pathway.
“Rhythm’s integrated translational approach is deepening the understanding of how the MC4R pathway contributes to obesity and identifying patient populations who may benefit from targeted pharmacotherapies.”
— Alastair Garfield, Ph.D., Head of Translational Research
Rare genetic diseases of obesity are distinct from general obesity, and are characterized by early-onset, severe obesity and insatiable hunger, known as hyperphagia. Specifically, Rhythm’s unique focus is on rare genetic diseases of obesity that are caused by genetic deficiencies within the MC4R pathway.
We believe that more meaningful therapeutic options can be found with a deeper understanding of the genetics that influence energy balance and body weight. Body weight is defined by the balance between energy intake (in the form of calories) and energy expenditure (basal metabolic rate, thermogenesis and physical activity).
Weight gain occurs when energy intake exceeds energy expenditure, leading to the storage of excess energy as fat. While many environmental factors can influence this balance, our genes also play a significant role in defining our body weight. Research has shown that some naturally arising genetic variants are associated with obesity. However, it’s important to note that the impact of these variants on body weight can vary considerably.
Rare genetic diseases of obesity arising due to MC4R pathway dysfunction are characterized by the hallmark characteristics of severe, early-onset obesity and hyperphagia.
Rare genetic diseases of obesity generally arise due to rare, highly impactful variants in just one gene that result in the loss of function of key energy balance regulating systems. The MC4R pathway is one such key system. Hyperphagia is characterized by an overwhelming, heightened, and relentless hunger, longer time to reach satiety, shorter duration of satiety, and potentially, extreme food-seeking behaviors. Examples of this include waking up at night to find food or eating non-food items. Hyperphagia leads to excess energy intake, which contributes to obesity. There are currently no approved therapies for the treatment of hyperphagia and obesity associated with rare genetic diseases of obesity.
The MC4R pathway regulates hunger, caloric intake, and energy expenditure, consequently affecting body weight.
Rhythm is building the largest database of DNA sequences from individuals living with severe obesity to improve the understanding of MC4R pathway related diseases.
Rhythm is focused on rare genetic diseases of obesity which may be caused by an impaired MC4R pathway.
Rhythm is developing setmelanotide, an investigational MC4R agonist in late-stage clinical development for the treatment of rare genetic diseases of obesity.
Clinical studies are a type of medical research designed to better understand a disease. They can also explore different ways to treat a health condition, including developing new medicines that aren’t currently available.
Expanded access is the use of an investigational therapy outside of clinical trials to treat patients with serious or immediately life-threatening diseases
or conditions when there are no comparable or satisfactory alternative treatment options.