Science Overview

Our Science​

Rhythm is dedicated to understanding rare genetic diseases of 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.”

— Patrick Kleyn, Ph.D., SVP and Head Translational Research and Development

Not all obesity is the same.

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 variants within the MC4R pathway.

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

*image is not scaled to size

Rare genetic diseases of obesity arising due to MC4R pathway dysfunction are characterized by the hallmark characteristics of early-onset, severe 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.

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 rare genetic diseases of obesity which may be caused by impaired signaling of the MC4R pathway.