Science Overview

Our Science​

Rhythm is dedicated to understanding hyperphagia and severe obesity caused by impaired signaling in the central pathway of 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.”

— David Meeker, M.D., CEO

Not all obesity is the same.

Rhythm’s unique focus is on MC4R pathway diseases. Diseases of obesity caused by rare MC4R pathway impairments are distinct from general obesity, and are characterized by early-onset, severe obesity and pathological, insatiable hunger, known as hyperphagia.

Obesity is the result of factors that disrupt the balance of energy intake (food consumption) and energy expenditure (metabolic rate, thermogenesis, and physical activity).

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.

Rhythm is focused on a subset of individuals living with severe forms of obesity

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Diseases of obesity due to MC4R pathway dysfunction are characterized by the hallmark characteristics of early-onset, severe obesity and hyperphagia.

The melanocortin-4 receptor (MC4R) is known to be a critical component in the regulation of energy balance. Variants in genes in the MC4R pathway or injury to the hypothalamic region may impair pathway activation which can lead to hyperphagia (pathological, insatiable hunger) and severe obesity.

Hyperphagia is characterized by an overwhelming, heightened, and all-consuming 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. Hyperphagia leads to excess energy intake, which contributes to obesity.

MC4R Pathway

The MC4R pathway regulates hunger, caloric intake, and energy expenditure, consequently affecting body weight.

Our Research

Rhythm is building the largest database of DNA sequences from individuals living with severe obesity to improve the understanding of MC4R pathway related diseases.

Our Focus

Rhythm is focused on severe obesity and hyperphagia caused by impaired signaling of the MC4R pathway.