Understanding rare melanocortin-4 receptor (MC4R) pathway diseases

The MC4R pathway plays a pivotal role in the underlying biology of many forms of severe hyperphagia and obesity. We are committed to using our growing understanding of this pathway to develop new therapeutic options…to relieve the substantial burden of living with these rare diseases.

Alastair G.

Not all obesity is the same

Rare diseases caused by MC4R impairment can lead to different forms of obesity that present with:

  • Hyperphagia: an insatiable, pathological hunger that can lead to abnormal food-seeking behaviors
  • Severe obesity (can include either of the following):
    • Early-onset, severe obesity: obesity presenting in young children caused by impairment of the MC4R pathway in the hypothalamus
    • Rapid-onset, severe obesity: dramatic weight gain in a short period of time caused by injury to the hypothalamus

The MC4R pathway

The MC4R pathway in the hypothalamus is responsible for regulating hunger, caloric intake, and energy expenditure. When impaired, it can lead to rare MC4R pathway diseases characterized by hyperphagia and obesity.

MC4R pathway impairment and hyperphagia

MC4R pathway impairment can cause hyperphagia, a pathological, insatiable hunger that has a significant impact on patients and their families.

Symptoms of hyperphagia may be extreme and constant. Hyperphagia is accompanied by abnormal food-seeking behaviors, which may include waking up at night to find food, eating food others leave behind, and, in severe cases, sneaking, stealing, or hiding food. Food-seeking behaviors and symptoms of hyperphagia can be overwhelming and relentless, and hyperphagia brought on by impairment of the MC4R pathway leads to severe obesity.

Rhythm is uniquely focused on discovering new treatments that may offer hope and an improved quality of life for patients with hyperphagia caused by MC4R pathway impairments due to genetic variants or hypothalamic damage.

Discover more

Learn more about hyperphagia and severe obesity, how rare MC4R pathway diseases are diagnosed, and where to find help and support.