How Do Alpha-Melanocyte Stimulating Hormone Analogs Work?

Alpha-melanocyte-stimulating hormone (MSH) analogs are a class of drugs used to treat erythropoietic protoporphyria (EPP). EPP is one of the painful cutaneous porphyrias (a group of genetic diseases in which there are enzyme deficiencies in the heme pathway; heme is a part of hemoglobin that gives blood its red color) due to an inherited deficiency of the enzyme ferrochelatase. Reduced activity of this enzyme causes a build-up of protoporphyrin in the skin resulting in photosensitivity. It typically manifests in early childhood as painful photosensitivity (one to 20 minutes of sun exposure causes burning pain on the exposed skin). Males and females are equally affected.

The MSHs also known as “melanotropins” are a family of peptide hormones and neuropeptides consisting of α-MSH, β-MSH, and γ-MSH. These hormones are produced by the skin, pituitary gland, and hypothalamus. They play a key role in producing colored pigmentation in the skin, hair, and eyes. When exposed to ultraviolet radiation, the production of MSH is enhanced by the specialized skin cells called “melanocytes,” which produce a pigment called melanin that is responsible to protect cells from DNA damage that can lead to skin cancer (melanoma).

α-MSH analogs are administered as a subcutaneous implant and they work in the following ways:

• They bind to the melanocortin-1 receptor and stimulate melanocyte proliferation and melanogenesis (production of the melanin pigments).
• They stimulate the production of eumelanin (a form of melanin) in the skin—a tanning pigment that induces antioxidant activities, enhances DNA repair process and controls inflammation.
• Melanin production is stimulated by exposure to UV radiation that can cause cellular damage, which in turn increases the risk of skin cancer.
• In addition, melanin has antioxidant activity that protects the skin from free radicals. Free radicals are unstable atoms that can damage cells, causing illness and aging.

They are implanted under the skin, usually around the hip, inserted by a specialist physician every 2 months; it is recommended to have 3 implants per year, with a maximum of 4 per year. You may feel the implant through the skin, but it does not cause pain or discomfort; the implant will dissolve in the body over time.

Conditions treated with α-MSH analogs include:

• Phototoxicity (rendering the skin susceptible to damage upon exposure to light)
• Erythropoietic protoporphyria
• Vitiligo (a disease that causes loss of skin color in patches)
• Solar urticaria (a rare form of chronic physical or inducible urticaria characterized by itch, weal, and flare within minutes of sunlight exposure)
• Polymorphic light eruption (skin rash triggered by exposure to sunlight or artificial ultraviolet light)
• Hailey-Hailey disease (a rare genetic disorder that is characterized by blisters and erosions most often affecting the neck, armpits, skin folds, and genitals)

Common side effects include:

• Hyperpigmentation/pain/redness/itching at the implant site
• Skin irritation
• Mild tiredness
• Nausea
• Headache

Other rare side effects include:

• Scarring or a hard lump at implant site
• New moles or hair growth
• Dizziness (feeling faint, weak, or unsteady)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Drug names include:                              

• Afamelanotide
• Scenesse