Description

Setmelanotide: Understanding POMC, PCSK1, and LEPR Deficiencies

What Are POMC, PCSK1, and LEPR Deficiencies?

POMC, PCSK1, and LEPR deficiencies are rare genetic disorders that cause a severe form of obesity. They result from a genetic mutation inherited from both parents, disrupting the brain’s ability to regulate hunger.

Symptoms and Impact on the Body

POMC Deficiency (Pro-opiomelanocortin)

• Brain: Insatiable hunger (hyperphagia) and obesity
• Endocrine: Adrenal insufficiency, hypothyroidism, hypoglycemia, growth hormone deficiency
• Reproductive: Delayed puberty (hypogonadotropic hypogonadism)
• Other: Fair skin, red hair, liver failure

PCSK1 Deficiency (Proprotein Convertase Subtilisin/Kexin Type 1)

• Brain: Insatiable hunger (hyperphagia) and obesity
• Digestive: Gastrointestinal disorders (diarrhea from birth)
• Kidneys: Acid accumulation, excessive thirst
• Endocrine: Diabetes, hypoglycemia, cortisol deficiency
• Other: Infant growth delay

LEPR Deficiency (Leptin Receptor)

• Brain: Hyperphagia and obesity
• Endocrine: High insulin levels
• Reproductive: Delayed puberty
• Other: Diabetes

Understanding Hyperphagia

The hyperphagia associated with these deficiencies is uncontrollable and differs from typical overeating. It is characterized by:

• Constant hunger, even after meals
• Obsession with food
• Compulsive food-seeking behavior

Treatment: How Does Setmelanotide Work?

Setmelanotide is a treatment designed to restore the function of the MC4R pathway, helping to regulate the feeling of satiety.

Clinical Effectiveness

Studies have shown significant weight loss and reduced hunger in treated patients:

• POMC/PCSK1: 80% of patients lost at least 10% of their body weight within a year
• LEPR: 45% of patients lost at least 10% of their body weight within a year

Administration

• Daily subcutaneous injection
• To be taken in the morning, with or without food

Possible Side Effects

The most common side effects include:

• Injection site reactions (96%)
• Skin darkening (78%)
• Nausea, headaches, fatigue, gastrointestinal issues

Conclusion

Setmelanotide represents a major advancement in managing POMC, PCSK1, and LEPR deficiencies. If you or a loved one are affected, consult your doctor to learn more about this treatment option.